Title: Amino cidos y P ptidos Amino cidos alfa -amino cido: glicina
1Aminoácidos y Péptidos
2Aminoácidos
Los aminoácidos son compuestos bifuncionales,
contienen un grupo amino básico y un grupo
carboxilo ácido. Se nombran según la posición
relativa de dichos grupos
Estructura general de un ?-aminoácido
Tienen valor como bloques biológicos porque
pueden formar péptidos entre el NH2 de un
aminoácido y el COOH de otro mediante enlaces
amida
3La Glycina es el aminoácido más simple y el único
que es aquiral. Para el resto, el carbono ? es
un centro de quiralidad.
4Síntesis de aminoácidos
5- Uno de los métodos más viejos data del siglo
diecinueve y es simplemente una sustitución
nucleofílica en la cual el amoníaco reacciona con
un ácido alfa halocarboxílico.
6Síntesis de Strecker
7Síntesis del ester malónico modificada
Sigue una hidrólisis
8Péptidos
9El enlace peptídico
Enlace peptídico
10- Por conveción, los péptidos se escriben tal que
el grupo amino está a la izquierda y el grupo
carboxilo a la derecha.
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12Análisis de aminoácidos
13- The chemistry behind amine acid analysis is
nothing more than acid-catalyzed hydrolysis of
amide (peptide) bonds. The peptide is hydrolyzed
by heating in 6 M hydrochloric acid for about 24
h to give a solution that contains all the amine
acids. This mixture is then separated by,
ion-exchange chromatography which separates the
amine acids mainly according to their acid-base
properties.
14Hidrólisis parcial de aminoácidos
- Trypsin, a digestive enzyme present in the
intestine, catalyzes only the hydrolysis of
peptide bonds involving the carboxyl group of a
lysine or arginine residue. - Chymotrypsin, another digestive enzyme, is
selective for peptide bonds involving the
carbexyl group of amine acids with aromatic side
chains (phenylalanine, tryrosine, tryptophan). - Carboxypeptidases, catalyzes only the hydrolysis
of the peptide bond to the C-terminal amine acid.
In addition to these, many other digestive
enzymes are known and their selectivity exploited
in the selective hydrolysis of peptides.
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16Análisis del grupo terminal
- As we saw in the preceding section,
carboxypeptidase-catalyzed hydrolysis cleaves the
C-terminal amino acid and so can be used to
identify it. What about the N terminus?
17- The N-terminal amino group is free and can act as
a nucleophile. Sanger's method for N-terminal
residue analysis involves treating a peptide with
1-fluoro-2,4-dinitrobenzene, which is very
reactive toward nucleophilic aromatic
substitution.
18Reactivo de Sanger
19- The amino group of the N-terminal amino acid
displaces fluoride from 1-fluoro-2,4-
dinitrobenzene and gives a peptide in which the
N-terminal nitrogen is labeled with a
2,4-dinitrophenyl (DNP) group.
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21La degradación de Edman
- A peptide reacts with phenyl isothiocyanate to
give a phenylthiocarbamoyl (PTC) derivative - This PTC derivative is then treated with an acid
in an anhydrous medium to cleave the amide bond
between the N-terminal amino acid and the
remainder of the peptide. - When the PTC derivative is treated with acid in
an anhydrous medium, the sulfur atom of the CS
unit acts as an internal nucleophile, and the
only amide bond cleaved under these conditions is
the one to the N-terminal amino acid. - The product of this cleavage, called a
thiazolone, is unstable under the conditions of
its formation and rearranges to a
phenylthiohydantoin (PTH), which is isolated and
identified by comparing it with standard samples
of PTH derivatives of known amino acids.
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23Síntesis de péptidos
24Protección del grupo amino
25- Z se puede remover fácilmente mediante
hidrogenólisis en presencia de paladio
26- A related N-terminal-protecting group is
tert-butoxycarbonyl, abbreviated Boc
27- Like the benzyloxycarbonyl protecting group, the
Boc group may be removed by treat- ment with
hydrogen bromide (it is stable to hydrogenolysis,
however)
28Protección del grupo carboxilo
- Carboxyl groups of amino acids and peptides are
normally protected as esters. Methyl and ethyl
esters are prepared by Fischer esterification.
Deprotection of methyl and ethyl esters is
accomplished by hydrolysis in base. Benzyl esters
are a popular choice because they can also be
removed by hydrogenolysis. Thus a synthetic
peptide, protected at both its N terminus with a
Z group and at its C terminus as a benzyl ester,
can be completely deprotected in a single
operation.
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30Formación del enlace peptídico