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Hemoglobin as Receptor for Drugs: Stereochemistry of Bonding

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 Perutz, Max

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Hemoglobin as Receptor for Drugs: Stereochemistry of Bonding
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spaceplay / pause qunload | stop ffullscreen shift + ←→slower / faster (latest Chrome and Safari) ↑↓volume mmute ←→seek . seek to previous 12…6 seek to 10%, 20%, …60% Max Perutz (1986) Hemoglobin as Receptor for Drugs: Stereochemistry of Bonding Comment Max Perutz was one of the founding fathers of X-ray crystallography – and a pioneer of medicinal chemistry. „I shall be very happy to continue my collaboration with you and do X-ray crystallography analyses of the binding sites of potential antisickling drugs that you develop“, Max Perutz wrote in a letter to Donald Abraham, a chemist from the University of Pittsburgh, on February 3, 1984. „This work is now entering a very interesting phase. By determining difference electron density maps of a variety of known drugs and of new synthetic compounds, the various possible binding sites in haemoglobin are being mapped, and are falling into some kind of order.“[1] Perutz and Abraham had first met at an Airlie House conference in Washington in 1980. Abraham had been a student of Alfred Burger, the founder of The Journal of Medicinal Chemistry in the 1960s. In the 1970s he had begun to focus his research on the rational design of drugs to treat sickle cell disease by targeting hemoglobin. He was quite isolated in his efforts, however. So he plucked up courage and approached the Nobel Laureate who reacted very positive: „My spirits rose to the heavens“, Abraham later recalled. „I was invited to the best laboratory in the world, not with recommendation letters or CV, but on an idea. This I learned was a hallmark of Max’s genius. Good ideas, whether his or others, were treasured. Formalities were not to stand in the way...“.[2] Between 1980 and 1988, Abraham visited the Laboratory of Molecular Biology in Cambridge 16 times, and Perutz was appointed to a visiting lectureship at the University of Pittsburgh from 1983 to 1986. In this year, Max Perutz held his first lecture (in German language) in Lindau – and offered fascinating insights into his collaboration with Abraham and their groundbreaking studies of how small molecules bind to proteins. The “wonderful method of computer graphics” was instrumental for these studies and during his lecture Perutz shares his enthusiasm for this innovation, which makes chemistry “beautiful and easy”, in a movie of about ten minutes length. It shows “for the first time the stereochemistry of the interactions between different drugs and a protein” and is much applauded. Even if one cannot see the movie in this audio file, Perutz’ comments are clear enough to catch its content by listening. Sickle cell anemia is caused by a point mutation in the beta-chain of haemoglobin. A single hydrophilic residue (glutamic acid) is replaced by a hydrophobic one (valine). This leads to a polymerization of hemoglobin at low oxygen tensions and consequently to a deformation of red blood cells during systemic circulation. The deformed erythrocytes may obstruct the blood flow in capillaries. Increasing the oxygen affinity of sickle cell hemoglobin by allosteric regulation of the mutated protein could offer a possibility to treat the disease. In this regard and supported by hematologists at the INSERM in Paris, Perutz and Abraham explored the structural interaction between hemoglobin and three drugs that already had been approved for different indications, namely the lipid-lowering agents clofibrate and bezafibrate and the loop diuretic ethacrynic acid. For different reasons, which Perutz describes in detail, all three drugs failed to become antisickling drugs. Nevertheless, Perutz’ observations nurtured the field of medicinal chemistry: “A drug can shift the allosteric equilibrium within a protein receptor into the same direction as the natural effector, although chemically not related to it (…) This is due to the fact that protein molecules are so large that they offer a lot of binding sites, which are not used by nature and hence can be harnessed for pharmacological effects.” Joachim Pietzsch [1] What a time I am having: selected letters of Max Perutz. Edited by Vivien Perutz. Cold Spring Harbor, 2009, p. 386f [2] Donald Abraham, Reminiscences, quoted from: Georgina Ferry. Max Perutz and the secret of life. London 2007, p. 237
00:00
NobeliumBukett <Wein>Elektronische ZigaretteNahtoderfahrungMolekülstruktur
00:49
Besprechung/Interview
01:46
BenetzungMagmaMannoseNeotenieKristallographieBesprechung/Interview
02:44
NobeliumHämoglobin FKristallographieBesprechung/Interview
03:41
Hydroxybuttersäure <gamma->Chemische ForschungBesprechung/Interview
04:38
Chemische ForschungBukett <Wein>PlasmamembranProteineAlpha-1-RezeptorPharmazeutische IndustrieBesprechung/Interview
05:36
PulverEukaryontische ZelleDNS-SyntheseIdiotypGlobineGenSekundärstrukturBesprechung/Interview
06:33
MagmaEukaryontische ZelleBiosyntheseBesprechung/Interview
07:30
SeltenerdmineralienEukaryontische ZelleMannoseBesprechung/Interview
08:28
Eukaryontische ZelleBesprechung/Interview
09:25
AdamantanEukaryontische ZelleWursthülleQuarz <alpha->Hämoglobin FBesprechung/Interview
10:22
Minimale HemmkonzentrationPolymereMolekülChemische StrukturEukaryontische ZelleHämoglobin FBesprechung/Interview
11:20
Hydroxybuttersäure <gamma->Eukaryontische ZelleValinBesprechung/Interview
12:17
Hämoglobin FElektronische ZigaretteGangart <Erzlagerstätte>ValinSulfideBesprechung/Interview
13:15
Hämoglobin FPhenylalaninEukaryontische ZelleKonzentratCobaltoxideLaborzentrifugeBesprechung/Interview
14:12
SymptomatologieEukaryontische ZelleHämoglobin FPolymereChemische ForschungPhenylalaninSäureBesprechung/Interview
15:09
Funktionelle GruppeBenzylgruppeChlorOrdnungszahlSäureHämoglobin FKonzentratBesprechung/Interview
16:07
ArzneimittelFunktionelle GruppeStoffgesetzBesprechung/Interview
17:04
Aktivität <Konzentration>Hämoglobin FKonzentratStoffgesetzCarbonylverbindungenFunktionelle GruppeAmine <primär->ThiolgruppeHistidinBesprechung/Interview
18:01
Funktionelle GruppeEukaryontische ZelleThiolgruppeAmine <primär->Besprechung/Interview
18:59
MagmaThiolgruppeBesprechung/Interview
19:56
ThermoformenProteinePharmazieBesprechung/Interview
20:53
AmpicillinHämoglobin FKetoneAlphaspektroskopieMolekülBesprechung/Interview
21:51
Hämoglobin FBesprechung/Interview
22:48
Setzen <Verfahrenstechnik>RegulatorgenBesprechung/Interview
23:46
MolekülEtomidatHämoglobin FWachsBesprechung/Interview
24:43
MagmaElektronische ZigaretteDipol <1,3->ChlorAtomWachsBenzolringThermoformenBesprechung/Interview
25:40
FFFMagmaElektronische ZigaretteAmine <primär->Dipol <1,3->AmineElektronegativitätAtomBesprechung/Interview
26:38
SpektroelektrochemieProteineAromatizitätGangart <Erzlagerstätte>PhenylalaninEtomidatIsobutylgruppeWachsBesprechung/Interview
27:35
KonvertierungArgininIsobutylgruppeCarboxylierungGuanidinGangart <Erzlagerstätte>Elektron <Legierung>Besprechung/Interview
28:32
PasteFunktionelle GruppeElektron <Legierung>Valenz <Chemie>KonformationsisomerieBindungsenergieThermoformenBesprechung/Interview
29:30
Valenz <Chemie>AtomPharmakologeDipol <1,3->Elektronische ZigaretteMethylgruppeFunktionelle GruppeBesprechung/Interview
30:27
ProteineDipol <1,3->Elektronische ZigaretteMethylgruppeCarboxylateBesprechung/Interview
31:24
PentapeptideCarboxylateProteineRauschgiftSerinElektronische ZigaretteHydrocarboxylierungAromatizitätBesprechung/Interview
32:22
CarboxylierungCarboxylateElektronische ZigaretteMethylgruppeTryptophanFunktionelle GruppeMolekülBesprechung/Interview
33:19
HalbedelsteinISO-Komplex-HeilweiseBesprechung/Interview
34:16
Funktionelle GruppeBesprechung/Interview
35:14
DeferoxaminAtomBesprechung/Interview
36:11
OxycodonZusatzstoffProteineHämoglobin FEukaryontische ZelleBesprechung/Interview
37:09
KonzentratElektrolytische DissoziationHämoglobin FBesprechung/Interview
38:06
ErdölraffinationElektrolytische DissoziationHämoglobin FEukaryontische ZelleBesprechung/Interview
39:03
SonnenschutzmittelBaseBesprechung/Interview
40:01
MagmaPhysiologieProlinMolekülHämoglobin FErdölraffinationFunktionelle GruppeImpfung <Chemie>SonnenschutzmittelLeucinBesprechung/Interview
40:58
Hydroxybuttersäure <gamma->Funktionelle GruppeLeucinErdölraffinationRauschgiftAromatizitätBesprechung/Interview
41:55
Funktionelle GruppeQuarz <alpha->Hämoglobin FElektron <Legierung>Besprechung/Interview
42:53
DarmstadtiumElektronische ZigaretteGangart <Erzlagerstätte>Elektron <Legierung>Chemische StrukturMagnetisierbarkeitMesomerieBesprechung/Interview
43:50
ProteinePentapeptideQuellgebietStereochemieWachsErdölraffinationAlpha-1-RezeptorRauschgiftEukaryontische ZelleAllosterischer EffektorBesprechung/Interview
44:47
Eukaryontische ZelleBindungsenergieAlpha-1-RezeptorProteineStereochemieQuellgebietPharmakologeBesprechung/Interview
45:45
Eukaryontische ZelleGangart <Erzlagerstätte>AromatizitätBesprechung/Interview
46:42
HühnergottPhysiologieGibbs-EnergieHyperpolarisierungAtomBesprechung/Interview
47:40
HyperpolarisierungProteineFunktionelle GruppeDerivateBesprechung/Interview
48:37
Chemische ForschungProteineTafelweinNobelium
Transkript: Englisch(automatisch erzeugt)
00:16
I'd like to start with the dominant hand. Last year I didn't know that the Nobel Prize winner
00:23
was the Olympic winner of the second World Series, his own winner. I skipped a hundred of the other thousand World Series winners and the only good winner was the Nobel Prize winner. But that was the end of the round, since there was not one Nobel Prize winner
00:41
or one Nobel Prize winner in the press, near Wabenham. Since the end of this round was the summer event in Munich, it was one of the most theoretical physicists who, in Munich, had a problem with the shoe-leggings. And there, in the year 1912,
01:02
during this attempt, Paul Ewald decided to assault Emil Aussrichtlin, who, we can't say that's a bad thing,
01:41
to be honest with you, because none had a word on this dissertation. He worked on it, and he said that this is a statement with a young man in Sommerfeldschen Institute who was working with the law. And the law, I believe, and, of course, there was a problem.
02:01
And, of course, he said, you should have a crystal, Emil, in a Röntgenstahl section and then a photographic plate at the intersection. Then, at the same time, a young man in a Röntgenstahl section came along. And that made him, then, very happy and happy.
02:21
I think that one of the Sommerfeldschen Institute and another Röntgenstahl Institute were the most ordinary, physical people in 1912. And then, at the same time, a Röntgenstahl section of the photographic plate came along, and that was the Röntgen crystallography.
02:42
And that was not the Sommerfeldschen Institute. There were no problems. They were not the Nobel Prize winners. And the law, the dissertation, was not the law, it was not just one of them.
03:00
But the other two, the Röntgenstahl and Sommerfeldschen Institute, were also very happy, and of course, Ewald Stapf in the last year, in the 19th year in Ithaca, New York. And I also want to talk about the Röntgenstahl crystallography
03:22
of the development of pharmacosporation in the hemoglobin. Since I am a chemist, I am a student of the 19th century, I have been working with the romantic scientists from Paul Ehrlich. Paul Ehrlich,
03:41
he was the one that was the first neuro-paraportist to work with one of the first medical experts and that was also, for instance, 60,000 years ago. And so on.
04:28
And how does it work? Not only in the pharmaceutical industry, but also in the industry. For example, if you have only 14,000 chemicals in your system, you must have at least one chemical that you can bring to the market.
04:46
Therefore, you have to bring the very first six years, four years, and the very long tests that you make, you have to have the cost for the individual chemicals of $60 million per year,
05:01
and start the next 10 years. And the point is that you have to bring them here. I mean, the pharmaceutical industry has a receptor, the receptor is a membrane protein, membrane proteins are very useful. Here is also an argument,
05:21
and also a special argument, that this is a receptor, this is a receptor in the body. In fact, I already said that this is a receptor in the body. And the stereochemistry, especially in the pharmaceutical industry,
05:41
and the receptor, you can find in the pharmaceutical industry, you can find this in the body, and you can find pharmaceuticals in the DNA. I think this is a very difficult question, and I think that this is a very difficult question.
06:00
This is the problem of the cell anemone. The cell anemone is a very small cell anemone, and it comes to the question of a mutation in one of the genes of the amino sequence in the globin cell. I think that
06:21
if you have malaria in Africa, and you find it in other malaria in the world, and you find it in Africa, you can find it in other countries, in different countries,
06:41
in different countries. If you find it in the first place, you can find it in the first place, and you find it in a cell with a cell anemone, and you see that it is a very abnormal cell. And this comes to the question of whether this cell is a very small cell,
07:02
and I am very happy to believe that the synthesis of the blood cell is a very small cell, and that the small, concentrated cell is a very small cell in the cell.
07:22
However, in my son's case, he is a very small cell, and he is very strong. The small cell is not small. In Malaria, in Africa, 50% of the cells are small. The small cell anemone is small.
07:42
I mean, when two of these cells are small, it is the choice that every 40 years, the small cell has, and that of a young man. I mean, not only the small cell, but the small cell in America, and in North and Middle America,
08:03
also a big problem. So, in the 80s, there was a conference in Washington, and I came to see my son, and I came to see him, under a victim from a farmhouse under a single cell anemone,
08:22
and I saw him in his house. And he thought that the small cell was small. And I thought that the small cell was small, and that the small cell was small, and that
08:41
the small cell was small. So, I thought the cell was small, and we understand that the small cell was small, and that the small cell
09:01
was a small cell. First, we came to understand that the next cell is a normal cell. I thought that it was a small cell, two small cells, with a ring in the middle,
09:21
and here is a small cell, the small cell. Why? Well, this is a case that hemoglobin in the blood cell is used to be crystallized. And what?
09:41
Crystallization is used in the form of long-term the hemoglobin polymerized in the blood cell in the form of long-term that the small cell is a small cell, so that the small cell is strong. And then, in the
10:00
small cell, the small cell, or the small cell, the cell is a small cell in fact. And this is a fact that we have to understand. We came to understand that the next cell
10:20
is a small cell. I thought that this cell is a hemoglobin molecule with a small cell and the polymerization is a small cell with a long-term structure. Then, we came to
10:42
understand that the cell is a functional cell, with a small cell and a small cell with 300 small molecules of hemoglobin with a small cell
11:01
with a small cell with a small cell with a small cell with a small cell with a large cell
11:41
with a small cell with a small cell with an
12:09
And here, it is a good means of sex to get the valine assessed. And this is valine cleft, also. At the end of the valine, you can see the beta-kete.
12:24
And this way we can stabilize the polymer, the double-kete, and that way we can get it. So, here, we can see the valine, in the hemoglobin molecule, and the next step is to get a model. And then, the keten, which is this whole plate,
12:45
is the beta-kete. This means that the amino ends are beta-kete, the alpha-kete is the alpha-kete, and here, the beta-kete is the good means that the valine is assessed.
13:01
So, now, so far, for the first time in the cell, yet, we feel that one needs to get the keten, the alpha-kete, to get the sulfide. So, I'd like to ask you, does this phenylalanine, I don't know, I'm not sure, does this phenylalanine get sick of work?
13:23
How do you test it? Well, the test can only be done, it's very important. If you take the hemoglobin from the blood in the cell, which is the most isolated cell, and you take the blood,
13:40
so that it gets in the cell, I think it gets in the blood, so that when the blood is in the cell, the cell is in the cell, and when the hemoglobin is in the cell, 20% of the hemoglobin is in the cell, then the oxygenation of the hemoglobin is out,
14:01
the centrifugation is out, and then the hemoglobin concentration is in the cell, and we say we're 10% in the cell. And yet, since the cell is in the middle of the cell, the polymerization is behind it,
14:21
and therefore the concentration, the leucine, of 30% or 40% of the hemoglobin. I mean, if it's in the middle of the cell, in the middle of the cell, and in the middle of the cell, this middle can be done, and an index of the working cell, this middle cell. So, for example,
14:41
the chemical is in the middle of the cell, so I'm going to show you that in the next slide, and I'm going to talk a little bit about the phenylalanine. Then you have the question that it's possible for women to have a phenyl-oxy-Esic acid
15:03
because it's here. Not because here it's an acid acid, and here it's a benzyl, not a phenyl, a benzyl-oxy-Esic acid. And that the work is not possible if you have only two chloro atoms
15:20
in the benzyl ring. So, you have this function here, a relatively good function. However, it's possible for two. For instance, you have this new, not-covalent function,
15:41
and also you have a very strong function, or the Van der Waals-Welk's function, in the hemoglobin angle, and you see that there is a very high concentration of these metals, and my function gets bigger and bigger. And the second point, not because we're in an argument,
16:00
is that $16 million and 10 years later, a new middle of the market becomes. So, of course, my American friend, Dr. Don Abraham, Don Abraham, professor of medicine
16:22
at the University of Pittsburgh, of course, I don't know a lot of people from the Food and Drug Administration who are doing this, and a lot of people are doing this, and it's a gift that a little bit of the Constitution had.
16:40
And there are the close friends of the function. There is also a middle who is beautiful, who has the role of the world, for which it is. Since then, I don't know a little bit of the Constitution. And we find out that it's very much the same as my work.
17:02
However, I'd like to say that it's not only secondary because of the hemoglobin and because of the concentration. So, I'd like to say that it's not only a middle, but that I feel co-violent with the hemoglobin and the
17:21
whole Constitution. And that means that it is theoretical, the ethical theory, that an activity is being done. Since not only a carbonyl group that activates the dopamine so that the sulfhydryl group
17:41
or the histidine group or the amino group are co-violent. And that is also one of the middle that I see. Then I saw with a colleague in Cambridge Hospital
18:00
when the sulfhydryl group works together with the cell enemy. Then I feel that the sulfhydryl works together. Here I feel that the
18:26
sulfhydryl works together the amino group or the
18:42
sulfhydryl Then I feel that the sulfhydryl group works together with the amino group or the group. Then I feel that the sulfhydryl together with the
19:02
or sulfhydryl Then I feel that works or the sulfhydryl
19:20
group. Then feel that of dissertations, and opinions, and so on, and so on. So, this work was the three-line battle. I was from America, I was from Finland, I came back and I did the ranking histography,
19:40
and in Paris, I did the hematology. Yet, I got the result, and I saw a lot of them. I was in the ranking histography, and this is a wonderful method of computer graphics.
20:02
I can build the protein molecules, the strong molecules, in the form of a fancy film of computer graphics, and then I can see that people have to run, for growth, for growth, for one side and the other.
20:21
So, I came back and I saw a lot of them, and I saw a lot of them, and I saw a lot of them, and I saw a lot of them, and I saw a lot of them, and I saw a lot of them. I found a young chemist in the University of New York,
20:43
in England, Rob Hubbard, and the chemist was a computer programmer, an expert, and they had a program, a program of computer graphics, and we also saw in August,
21:02
this film here, that I didn't have enough time for. So, I can see the film here. The film takes the first, the first hemoglobin molecule, and takes it to the outside, it goes closer and closer and closer,
21:25
and you can see that it's hot, it has an alpha spherin in it. I saw the green in the beta, and the white in the alpha ketone, and here you can see the hemone, I saw the red plate, there are also four ketones and four hemones,
21:40
and the hemones, for instance, are very similar to that. And then, you can see that the molecule is very similar to the hemoglobin molecule. The hemoglobin is a dynamic molecule,
22:02
it is a mechanism, and here you can see the model, and you can see that it is an axial and a de-axial structure, and it is very similar, I saw it twice, it is one of the first hemoglobin molecules,
22:47
and this structure, I also saw it along with two other types of hemoglobin, and this structure, which is a very different type of hemoglobin, is called Grun-de-oxy, Grun-de-oxy, and Grut-oxy.
23:01
I saw that Grun-de-oxy is a very important molecule, and the Grut-oxy, and the Grut-oxy, the first type is the de-oxy structure, and there is also a switch, and in the switch there is a regulator, the de-phosphoglycerate,
23:27
which is essentially deoxy, which passes through, and in the deoxy there is a switch, and the regulator goes through.
23:42
This regulator stabilizes the deoxy structure, and it generates the same kind of affinity, the hemoglobin, in against the gas. It changes the first molecule first. Not the blood, the blood is in the beta-fibrate molecule.
24:02
Here you see the beta-fibrate. Here is the chlorine, the first benzene, the amide group, C-H-2, C-H-2, and C-H-2. And here you see the volume of the beta-fibrates. The reason is that the hemoglobin molecule in this molecule
24:21
is not connected to this gradient. Not what you see here. In the middle, in the inner, the hemoglobin molecule, and here you see the beta-fibrate. And when we are in the middle, the wax will come in,
24:42
switching the hemoglobin and the beta-fibrate. This is the swede, this is the wax. And we are finally here with the chlorine. Here is the chlorine atom,
25:00
and here is the atom. So the chlorine atom is a dipole, and the negative end of the dipole sits on chlorine, and this begins with the washer atom, and this is the positive end of the quatropoles, the benzene.
25:22
I am sure that this is the form of protein, and that the dipole moment, the drug, the quatropole, the protein, will be compensated with. So this is a small example.
25:41
Here is an asparagine, an asparagine group, and it begins with the amine group with the p-electrones, the pencil rings, the pharmacromes. And it begins with the asparagine, the dipole moment, from three to four, and the positive end is here.
26:02
So it begins with the positive end of the dipole, and with the negative end of the quatropole, the phenylalanine, and this is also a new atom, the washer atom, and the washer atom begins with the amine group, and the p-electrones, and the pencil rings.
26:23
Here you can see the washer atom, the aliphatic washer atom, with the alicene atom, and it begins with the amine group, not only with the electronegativity.
26:43
I've already told you that when PP wax works, the aromatics work on the proteins, so that the drug-designers work on the proteins. The next step is to make the washer atom,
27:03
the anion aromatic rings, with the p-electrones, the phenylalanine rings. The wax works are very polar, and here I've already told you the wax works, the polyne ring, the polyne ring, the polyne,
27:22
and the drug-designers work on the proteins. Here you can see the amide group, the isobutyl group. I've already told you the rhesium, the phenylalanine ring, and I've already told you the washer atom, the carboxyl group,
27:43
and the guanidine group, the arginines. The electron, of course, is the isobutyl group, the undifferentiated kugel, so that we can't see how it works. The next step is to make the eta-creams.
28:02
Here's the reactive-hoc-reactive atom, and I've already told you that. The eta-creams are paired with the sulfidryl group, the cysteines, which are also called tenispelic, that's one, and that's the other.
28:22
The electron is connected to the eta-creams, in this slits here in the past, and we're still trying to figure it out. Here's the electron group, and here's the sulfidryl group,
28:40
here's the schwafel atom, here's the hemene group, that's one, is osculacin, that's the rhesin-salt, and here's the form, the electron group in the past. I've already told you that this is the clear atom,
29:01
and here's the binding. Here's the form of the eta-creams, in the conformation of the adenine, and here's the reactive-hoc-reactive atom, here's the valence volume, and here's the im-protein adenine,
29:24
and here's the second half of the valence volume of the eta-cream, that's one, and here's the valence volume of one atom in the ring, and this is the rho-g. This is the conformation,
29:41
here's the rho-g, we've got eta-creams, eta-creams, here's the hemoglobin, and here's the spitzel, and here's the eta-cream, and here's the pharmacase. So we're saying that the pharma doesn't have the entire filter, it requires a lot,
30:01
the layer is, and also the spitzel, also, the spitzel, the spitzel, this is the middle, in this case, there is a conch, and a methyl group, and a hydrogen group. So here's the plus and minus,
30:20
and also the negative end of the dipole is a little lower, and since the negative end of the dipole is associated with a histidine, this means that it is a positive atom, in fact. So now you see that
30:41
the dipole, the rho-g, is a positive atom, and this protein is compensated for it. So here's the positive end of the dipole, and this is the negative end of the carboxyl group
31:00
of the asparagus, compensated for it. So now we're going to see a little bit of a wonder-waltz, which we're going to see. So here's the methyl group of the dionine, which is here, and this is the therosine,
31:21
and I'll show you. So this is one of the things that is coming from a peptide, from a doctor in the Massachusetts Institute of Technology, this is the peptide group. This is the first link of the symmetry,
31:40
and this is the positive end of the protein. Here's the positive end of the carboxyl group of the proteins, this is the drug of a serine and a hopcaton of protein. Here's another one. Here's the last sentence.
32:01
What is the meaning of the carboxyl group of the carbonyl group, this is the last sentence, and the OH-group of the serine? I'm not sure if you saw the PP-Vexxer in the video, and in the video, you can see the little function, the aromatic ring is in the video,
32:21
this is the end of the carboxyl group, of one tryptophan is connected with the p-electron of the other end of the carboxyl group. This is the quadrupole of the carboxyl group. Here is the beta-3 group
32:42
with the end of the carboxyl group in contact with the methyl group and the end of the carboxyl group. And this is where the molecules are not connected to each other.
33:17
France is so proud, that it's not just the end of the carboxyl group.
33:22
Not yet, it came to the question, it came to the question, this method, the first minute, and the best specificity, the work can be done. And then, the second, you are comfortable winging the mobile network? You are comfortable winging the address
33:42
and I think the network will call you. immediately we award you Hawaii, that's very special. Then also, for public, we have the vested name of the diagram, that it is called the Carboxyl Group 3, and that says therounds of the trip
34:01
to the pi-identcal back of the Carboxyl Group 3 and in the last 40 years they've been working on it. And this is the last time they've been working on it. I think it's a wonderful experience. So, I'd like to tell you a little bit about the film. There was, in the beginning, a log.
34:22
And it was here. You can see that there was a log, and it had two groups here, one hanging, and the other. And the last two groups were hanging in the log. You can't see them anymore. Not only were they here, but also the log. And you can see that there were only two groups hanging here.
34:45
And the last group, in the end, you can see the cameras. You can't see them anywhere else. You can see the computer graphics. You can't see them anywhere else.
35:02
And I'd like to tell you a little bit about the inter-atomic distance between these two atoms, and one other atom, which is located in the center of the four angles. And in the second one, there is only one atom. I'd like to tell you a little bit about it.
35:22
So, after Abraham, after Abraham's death, I met him with a hemoglobin, a very crystalline, and when I met Linda, I met Abraham, and I saw the ring in his eyes, and I thought, well, that's very nice. So, I saw it.
35:40
And it was, in fact, very difficult to find hemoglobin. It was very difficult for me. And it was very difficult for me to find the anti-sicky ring, to find this ring. And it was difficult for me to find a good reaction,
36:02
that is, the six-cell polymer, to find the same hemoglobin, in the same cell. Each cell has its own affinity, or an anti-sicky ring.
36:21
And it is important to understand, that this ring, that this ring, is one of the most important proteins in the normal world, because it is the oxy hemoglobin stabilizer. Then, I saw in the first film, the beta-fibrate, and in the second film, in the second film,
36:41
in the third film, the beta-fibrate, is not the same, it is the same process, the same process, in a way, but, it is not the same concentration, the same affinity,
37:01
in the same way, and, especially in the clinic, I thought, well, that a farmer, or a farmer, who has the same affinity, is not necessarily the same, because, in fact, what is the same thing, and what is the same thing, in the same way, is the same.
37:21
So, there is a lot of interest, and, well, we have done better, we worked hard, and the next thing, is the effect of the same dissociation curve of hemoglobin, this is, from the beta-fibrate concentration. So, here is the logarithm
37:41
of the same process, the same process, in the second film, here is the logarithm of the same process, the same process, in the second film, the same process, I found, here is the dissociation curve, of the same hemoglobin. When we have 5,000 millimoles of beta-fibrate, then,
38:00
we have found, that the dissociation curve has reached what is a middle of the affinity of the cell. So, we had hemoglobin and a natural so-called effect that the force of the glycerin, the dissociation curve
38:22
is in the right direction of the dissociation
39:54
the basic fact-concentrations factor here failed. And the question is, in fact,
40:02
what are the methods used to find the affinity for this drug, for the hemoglobin molecule to help? So, shortly after I saw the computer graphics, and then we realized that this drug, a vaccine,
40:24
was made with a leucine, which is now Arginine, Proline... Yes, this is leucine. So, of course, we were very happy that we found a single group of this molecule
40:42
and then a group of leucines with an electrostatic, not an electrostatic vaccine of 72 kilocalorines to find the affinity for a certain factor of 100.
41:03
So, for example, I found this in computer graphics and, as you can see, the other group of leucines is now called Gebenkrante. And this is made from beringa in Mannheim,
41:21
and the beringa in Mannheim is now called an organica. And this is made, and then, of course, it is very likely that Gebenkrante is not able to find the affinity for this drug. Yet, there is not one way of looking at it. Since then,
41:41
we have seen, by the impetus, the STT, the succinyl tryptophan, tryptophan, that the aromatic ring is very important to us. And this is why the question is that it is an artifact, that when we have a hemoglobin molecule,
42:01
we store the ring in the right place, or in the left place. Therefore, there is a group of Massachusetts Institute of Technology, an analysis of a crystal of glycine,
42:21
L-phenylalanine, D-phenylalanine, and this is not the result, it is not built yet. Ah, here it is, here it is built from the STT, the succinyl tryptophan, tryptophan, and this is why I said,
42:40
we, this was the basis of the attack of the N in those rings, I made the pure electrons of the solar rings and I thought that, I thought that, in the right place, and in the left, the next step is to the crystal structure
43:03
of this glycine, phenylalanine, phenylalanine, and since that is in the crystal, we can now say that this is one of the solar rings with a pure electron in the right place and the solar ring is also there, so that I am the positive end
43:21
of the other quadrupoles with the negative end of the other quadrupoles and I, nuclear magnetic resonance, resonance of Angela Gronenborn and Max Planck Institute for Biochemistry in Martin Street,
43:40
thus the solar structure in Leuzen of the street. What is the argument of the four of you? I remember that first of all we saw the stereochemistry of the wax working in a drug, in a drug, in a peptide, and in a protein.
44:01
What is it? First of all, can I say a little bit more? A little bit more, please. What I forgot to say is that this peptide is also the source of the affinity of the star. So it is also
44:21
a very important thing to recognize the allosteric effect and, in the future, to find a way to get to the point with the hemoglobin for one. So, today, I would like to say that a drug
44:40
that allosterically works in a protein receptor in the cell which is also a natural receptor and also a natural effect and also
45:00
the natural effect in the cell and also a large amount of binding cells. And this is why this protein molecule is so big that it is a large amount of binding cell that in nature
45:22
cannot be noticed. And this is also the source of the pharmacology of the pharmacological effect in the cell. The other important thing is the stereochemistry of the cell.
45:41
The stereochemistry of the cell is the most important step in the world. And in this step, there is a very important part of the cell that in the cell. And
46:00
the second part is the natural effect in the And the third part is the natural
46:25
effect in the cell. of the aromatic ring. And I am looking forward to working with the aromatic quadrupole, and not only working with the aromatic ring, but also working with
46:41
the aliphatic ring. Linus Pauling, in the great American chemical, had two principles of the ring-wising, for a long time. The first one, which was the most important for the physiology of the ring,
47:01
is called the ring-wising. And the second one is the free ring-wising, which is a hapten, and an anti-carp, proportional to the sum of the polarizer that I call an atom. I want to say that the free energy
47:24
of the ring-wising is a hapten, and an anti-carp, proportional to the sum of the polarizer that I call an atom.
47:41
Our result is a three-discipline. Our result is a three-discipline. We have a pharmacome and a protein that is very, very, very, very, very, the sum of the electrostatic energy
48:03
of the ring-wising, proportional to the sum of the polarizer Our result is a three-discipline. This means that the ring-wising of the polarizer, which is an anti-carp, proportional to the sum of the polarizer.
48:20
Yet, when we have a ring-wising, we have a middle ring-wising. We have the most important result, which is a derivative of the ring-wising. The result is a function of the ring-wising. And then, I also want to say that this is a middle ring-wising.
48:48
The middle ring-wising is the same as the single ring-wising. And the single ring-wising is the same as the single ring-wising.