Peptides heteromeric

Scheme 13 Solid-Phase Synthesis of Heteromeric Peptide Dendrimers on a Di-K2K Dendron[2S1...

Innine ligation of unprotected peptides is based on the chemoselectivity between a weak base and an aldehyde to form either a stable imine or an imino intermediate that can isomerize rapidly to a more stable product. Whereas the thiol ligations are optimally performed at neutral or basic pH, imine ligations are performed under acidic conditions, which is highly desirable because under acidic conditions the basic side-chain nucleophiles of an unprotected peptide are protonated to be excluded from the reaction. Furthermore, these two reaction conditions can be exploited for ligating dissimilar peptide chains to a core to form heteromeric peptide dendrimers.11401... 

A worm-eating species, C. imperialis, produces a-conotoxin Iml, which is an effective antagonist of homomeric-type neuronal nicotinic receptors, such as rat a7 or a9 (reported IC50 values of 0.22 and 1.8 (jM, respectively). This commercially available 12 amino acid amidated peptide is a very weak blocker of mouse muscle receptors (IC50 = 51 jtiM) and is ineffective at 5 fiM on heteromeric rat neuronal receptors (259). 

Heteromeric peptides, peptides that also contain non-proteinogenic building blocks. 

Lipopeptides, peptides modified with lipid residues which are preferentially bound at the thiol function of cysteine or at the a-amino group of N-terminal amino acids. The a-subunits of heteromeric G proteins and non-tyrosine receptor kinases contain N-myristoylated N-terminal glycine residues together with S-palmitoylation of a neighboring cysteine residue. Lipid moieties are necessary to recruit and anchor peptides and proteins to the membrane. Furthermore, it has been postulated that lipidation of proteins represents an event in signal transduction. The synthesis of lipid-modified peptides is not easy to perform as all coupling and deprotection reactions must be carried out under very mild conditions [S. Moffet et al., EMBO J. 1993, 12, 349 D. Kadereit et al., Chem. Fur./. 2001, 7,1184]. 

Sanchez-Quesada, J. Isler. M.P. Ghadiri. M.R. Modulating ion channel properties of transmembrane peptide nanotubes through heteromeric supramolecular assemblies. J. Am. Chem. Soc. 2002, 124 (34). 10004-10005. 

P. which contain only amino acid residues are called homomeric P., whereas P. with non-amino acid constituents are known as heteromeric P. Each of these classes is further subdivided into homodetic P., which contain only peptide bonds, and heterodetic P, which contain other bonds, e.g. ester, thioether or disulfide. Heterodetic P. possessing one or more ester bonds as hetero link are called Depsipeptides (see). The classification of depsipeptides does not accord entirely with the homomeric/heteromeric system it has arisen from the fact that the synthesis of these peptides presents rather special problems. There are two types of homomeric depsipeptides O-peptides contain ester-linked hydroxyamino acids, and they may be linear or cyclic (i. e. lactones) in S-peptides or thiodepsipep-tides, the mercapto group of a cysteine residue is acy-lated with an amino acid. Heteromeric depsipeptides contain hydroxy acids as the hetero component, and they are also known as peptolides. P. with non-amino... 

Arguably, the best studied example of a two-component heteromeric coiled-coil fiber-forming system comes from our own lab. The self-assembling fibers (SAFs) consist of two different complementary sequences that are designed to assemble into an offset parallel coiled-coil dimer. This leads to a sticky-ended tecton for fiber assembly. This design is realized with two four-heptad peptides with sequences as follows ... 

Peptides containing just amino acids (often the less common amino acids) are called homeomeric peptides, and peptides containing other compounds are heteromeric peptides or peptoids. This group includes ... 

These terms, homeomeric peptides and heteromeric peptides, should not be confused with the terms, homopeptide and heteropeptide, which Blout and Linsley (77) used to designate peptides consisting respectively of a single type of amino acid or of several different types of amino acids. 

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 peptide circulin, which was isolated from a culture of Bacillus circulans (431) should be placed in the polymyxin group. This antibiotic, active preferentially on Gram-negative bacteria (430) is a cyclic, basic heteromeric peptide, containing, as do polymyxins, L-a,7-diaminobutyric acid, threonine, and an optically active isomer of pelargonic acid which is probably (-b)6-methyloctanoic acid. In addition, circulin contains D-leucine (458). The composition (Table IX) of circulin is close to that of polymyxins A and E. However, this antibiotic, unlike polymyxin A, is inactivated by the enzyme lipase (458). Paper chromatography (173) distinguishes circulin from polymyxins A and E. 

Polypeptin (398) is also related to the polymyxins. It is isolated from cultures of a mutant of B. circulans, B. krzemieniewski, and is a basic heteromeric peptide, with an isoelectric point at 11.0 and containing a, y-diaminobutyric acid. Polypeptin is distinct from the polymyxins by, among other things, the presence of a chromogenic ultraviolet-absorbing group (290). 

Park and Johnson (452) showed that acid-labile phosphorylated compounds accumulated in the cells of S. aureus H treated with low concentration of penicillin. Park (446) then isolated three nucleotides of uridine, possessing as a common basic unit uridine-5 -diphosphate, attached to an amino sugar (449). One of these nucleotides also possessed a peptide chain linked to the amino sugar, therefore a heteromeric peptide. This nucleotide-peptide was later isolated from antibiotic untreated staphylococci (447), in much lower yield. 

According to Woolley (654), lycomarasmin might contain an -hy-droxyalanine derivative. The toxin can therefore be looked upon as a N-(a-[ -hydroxypropionic acid])-glycylasparagine, which therefore classifies it as a heteromeric peptide. 

There are now five known peptides extracted from rye ergot, and they are classified into 2 groups (Table XII). They are all heteromeric polycyclic peptides, containing one molecule of lysergic acid (316,317). 

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