L-a,y-diaminobutyric acid

Kemp DS, Stites WE. A convenient preparation of derivatives of 3(S)-amino-10(R)-carboxy-l,6-diaza-cyclodeca-2,7-dione, the dilactam of L-a,y-diaminobutyric acid and D-glutamic acid a P-tum template. Tetrahedron Lett. 1988 29 5057-5060. 

Polymyxins. Polymyxin B [1404-26-8] and polymyxin E [1066-17-7] (colistin) are the only medically important antibacterials from a group of some thirty closely related cyclic decapeptide antibiotics in the polymyxin family, some of which are given in Table 2. Most family members contain a seven amino acid ring attached to a three amino acid tail, to which is attached a fatty acyl group. The octapeptins have a tail containing a single amino acid. Each antibiotic contains several L-a-y-diaminobutyric acid [1758-80-1], C4H10N2O2, (Dab) residues, L-threonine [72-19-5], at least one D-amino acid, and one of a very limited list of fatty acids. 

Molecular weight determination by the method of partial substitutional and spectrophotometric measurements of picrates gave values of about 1,360 for the hydrochlorides of both colistin A and B . Quantitative amino acid analysis showed the presence of six moles of L-a,y-diaminobutyric acid, two moles of L-threonine, one mole of L-leucine and one mole of D-leucine in both colistin A and By partial acid hydrolysis as well as by enzymatic... 

Polypeptin—Polypeptin was purified, crystallized as its sulphate and characterized by Howell . By means of coxmtercurrent distribution, Hausmann and Craig determined the components as L-a,y-diaminobutyric acid, L-threonine, D-valine, L-isoleucine, L-leucine and D-phenylalanine in the molar ratio 3 1 1 2 1 and an unknown fatty acid . The molecular weight of the free base was found to be 1,145. The structure of polypeptin is still unknown. 

Figure 5. Molar residue ellipticities of poly(L-a,Y-dianiinopropionic acid) [(DAP) ] at 250. Left 0.5 mM (DAP) (residue) in 50 mM NaDodS04 (-), NaDecS04 ( ) and Na0ctS04 (—) at neutral pH. Right 1.4 mM polypeptide (residue) in methanol at pH (apparent) 11.6. Poly(L-a,Y-diaminobutyric acid) [(DAB) ] is included for comparison. [Taken from Ref. (15) with permission by John Wiley Sons.]...

The polymyxins are antibiotic, basic, heteromeric peptides, which are active only against Gram-negative bacteria. They all contain L-a,Y-diaminobutyric acid, L-threonine, and (4-)6-methyloctanoic acid (55,114,... 

The circulins—As early as 1949, Peterson and Reineke characterized circulin as its sulphate. Total hydrolysis yielded D-leucine, L-threonine and L-a,y-diaminobutyric acid together with an optically active isomer of pelargonic acid. The existence of two components, found by Peterson and Reineke was later confirmed by the chromatographic separation of crude circulin into two major components, named circulin A and circulin B. In addition there was evidence for at least three other ninhydrin-positive, biologically active entities. In the hydrolysate of circulin A, L-isoleucine was found besides the amino acids previously reported . Quantitative amino acid analysis showed circulin A and B to be composed of L-a,y-diamino-butyric acid, L-threonine, D-leucine, L-isoleucine and ( + )-6-methyloctanoic acid in the molar ratio 6 2 1 1 1. After partial acid hydrolysis, fractionation and structure determination of the resulting peptides, circulin A and circulin B were formulated as cyclodecapeptides . Very recently, however, Japanese workers have revised the structure of circulin A. According to them, circulin A differs from colistin A only by a replacement of L-leucine in the latter by L-isoleucine Figure 1.7). 

The polymyxins—The members of the polymyxin group have very similar chemical and physical properties. They are all cyclic basic polypeptides containing characteristic constituents such as a,y-diaminobutyric acid, i,-threonine and a fatty acid. They differ by the presence or absence of the additional amino acids D-leucine, L-leucine, L-isoleucine, n-phenylalanine, D-valine and D-serine, as well as by the nature of the fatty acid Table 1.11). Their molecular weights are aU in the region of 1,200. Although several structural features had been established very early - the exact... 

The molecular weight of polymyxin B was shown by the method of partial substitution to be 1,150 d 10 per cent. Quantitative amino acid analysis yielded the amino acids a,y-diaminobutyric acid, L-threonine, D-phenylalanine and L-leucine in the molar proportions 6 2 1 1. Because no free a-carboxyl- and no free a-amino groups could be detected, polymyxin Bi had to be of a cyclic nature . Neither pepsin nor trypsin was found to attack the molecule and therefore partial hydrolysis and separation of the fragments was used for the elucidation of the structure. Of the 14 fragments isolated and identified, seven key peptides were necessary for proposing four tentative structures for polymyxin Two were formulated with a ring... 

Polymyxin B (C56H98Oi3Ni6 m.w.1202) is a cyclic peptide consisting for the major part of l-, < -, y-, diaminobutyric acid (5 residues), aside of L-threonine (2), L-leucine (1), D-phenylalanine (l),and (+)-6-methyl-octanoic acid (1). In order to be able to explain the formation of certain degradation products of this peptide it was first necessary to obtain some... 

Incorporation of the amino acids L-2,4-diaminobutyric acid (DAB) and homocysteine (HCY) into a PEA backbone was investigated with the aim of imparting stimuli-responsive degradation properties. Studies on model compounds revealed that the pendant y-amine or y-thiol of DAB and HCY esters experimented intramolecular cyclizalions at a much more rapid rate than background ester hydrolysis. Thus, stimuli-induced cyclization reactions (i.e., after deprotection of pendant groups by acids or reducing agents) were effective to cleave ester... 

AIB aminoisobutyric acid DAB (x,y-diaminobutyric acid DAP diaminopropionic acid DHA 2,6-diamino-7-hydroxyazelaic acid HIV D-2-hydroxyisovaleric acid ISER isoserine LAC L-lactic acid MO A 6-methyloctane acid (isopelargonic acid) MVAL iV-methyl-L-valine SP spermidine BTYR / -tyrosine mod, modified... 

A number of antibiotics contain amino acid residues that differ structurally from those found in proteins. Examples are ,y-diaminobutyric acid in the polymyxins, D- -aminoadipic acid in cephalosporin N and C, / -methyl-lanthionine in subtilin, nisin and cinnamycin, a-phenylsarcosine and L-a,lV-dimethylleucine in etamycin, (-)-)-, e-diamino-w-caproic acid ( 8-lysine) in streptothricini , and L-jS-methylaspartic acid (which can be formed from... 

Ac-E-L-E-K-L-L-X-E-L-E-K-L-L-K-E-L-E-K-amide, an amphipathic a-helical peptide, where X is substituted by leucine (LL7), valine (LV7), threonine (LT7), or serine (LS7), i.e., substitutions are made in the hydrophilic face of the helix cyclo-V-X-L-Y-P-V-X-L-Y-P), where X is substituted by diaminopropionic acid (Dap), diaminobutyric acid (Dab), ornithine (Orn), lysine (Lys), arginine (Arg), or histidine (His) Cyclo-(V-K-L-K-V-Y-P-L-K-V-K-L-Y-P), where 14 analogues were produced by single enantiomeric substitutions at each residue around the ring an extra two analogues were produced by double or quadruple enantiomeric substitutions of the lysine (K) residues... 

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