Peptides carboxylic acids

Proteases and peptidases 3.4.X.X peptides, carboxylic acids, esters, amides peptides, carboxylic acids, esters, amides >1000... 

During solid phase synthesis peptides are bound to the solid support by means of the C-terminal carboxyl group. The properties of the anchor group positioned between the growing oligomer and the solid support are crucial for the success of a solid phase synthesis. Usually, specialised linkers are used which provide either peptide carboxylic acids or peptide carboxylic amides upon cleavage [4]. A cleavage mechanism that proceeds by a nucleophilic attack... 

C Bromelain Pineapple stems Peptides Carboxylic acid... 

The Lessen reaction of peptide carboxylic acids has teen investigated in order to determine the carboxy terminal amino acid residue of peptides." The procedure first involves the formation of 0-pivaloylhydroxamic acids (187) by condensation of peptide carboxylic acids (184) with 0-pivaloylhy-droxylamine (185) using a water soluble carbodimide, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (186). The Lossen rearrangement of (187) occurs at pH 8.5 and 50 C to give a mixture of isocyanates (188) and their reaction products, which, on acidic hydrolysis, afford the aldehydes (189), ammonia and amino acids, as shown in Scheme 30." Identification of aldehydes determines the C-terminal amino acids of the original peptides. 

The substrate was composed of synthetic peptides, immobilized to a mica surface. The etching enzyme was Staphylococcal serine V8 protease, an enzyme that recognizes either glutamic or aspartic acid residues in the peptide and digests the peptides carboxyl acid terminus [1]. The enzyme was immobilized to the apex of an AFM probe, and the enzyme functionalized tip was scanned across the surface, in solution (phosphate buffer). 

The Chemical Synthesis of Peptides Carboxylic acids and acyl derivatives of the carboxyl functional group are very important in biochemistry. For example, the carboxylic acid functional group is present in the femily of lipids called fatty acids. Lipids called glycerides contain the ester functional group, a derivative of carboxylic acids. Furthermore, the entire class of biopolymers called proteins contain repeating amide functional group linkages. Amides are also derivatives of carboxylic acids. Both laboratory and biochemical syntheses of proteins require reactions that involve substitution at activated acyl carbons. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

Ammo acids are carboxylic acids that contain an amine function An amide bond between the carboxylic acid function of one ammo acid and the ammo nitrogen of another is called a peptide bond... 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

With its structure known, the synthesis of a peptide can then be undertaken— perhaps to obtain a larger amount for biological evaluation. A simple amide might be formed by treating an amine and a carboxylic acid with dicyclo-hexylcarbodiimide (DCC Section 21.7), but peptide synthesis is a more difficult problem because many different amide bonds must be formed in a specific order rather than at random. 

The mechanistic analogy to the Streckcr synthesis becomes obvious in the addition of the isocyanide to the imine to produce the a-amino nitrilium intermediate. Since all four components are involved in this step, it might be expected that every chiral component (chiral groups R1, R2, R3, R4) contributes to diastereofacial differentiation in the nucleophilic attack on the imine. However, in peptide syntheses by four-component condensation5, the chiral isocyanide or a chiral carboxylic acid component has only limited influence on the diastereoselectivity of the a-amino amide formation5. 

The effect of C ,C -disubstituted amino acids (aaAAs) on peptide secondary structure has been studied in recent years.2a d While longer side-chain C ,C -di-n-alkyl amino acids promote extended peptide conformation,23 alicyclic aaAAs, in which the Ca carbon forms a cyclic bridge with itself, such a 1-aminocyclopentane-l-carboxylic acid (Ac5c) and 1-aminocyclohexane-l-carboxylic acid (Ac6c), have helix-forming characteristics similar to those of 1 -aminoisobutyric acid (Aib).2ax... 

Schemes are available, however, that start from the free carboxylic acid, plus an activator . Dicyclohexylcarbodiimide, DCC, has been extensively employed as a promoter in esterification reactions, and in protein chemistry for peptide bond formation [187]. Although the reagent is toxic, and a stoichiometric concentration or more is necessary, this procedure is very useful, especially when a new derivative is targeted. The reaction usually proceeds at room temperature, is not subject to steric hindrance, and the conditions are mild, so that several types of functional groups can be employed, including acid-sensitive unsaturated acyl groups. In combination with 4-pyrrolidinonepyridine, this reagent has been employed for the preparation of long-chain fatty esters of cellulose from carboxylic acids, as depicted in Fig. 5 [166,185,188] ...

In 1996, research groups led by Gellman and Seebach, independently reported that enantiopure short chain y9-peptides with an appropriate substitution pattern (oligomer of /9-substituted /9-amino acids 1 [10] and oligomer of trans-2-amino-cy-clohexane carboxylic acid (trans-AGHG) 2 [6], respectively) could fold in a predict-... 

Fig. 2.7 Examples of constrained aminocycloalkane carboxylic acid derivatives for the synthesis of corresponding j8-peptides...

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