Polypeptides chemically modified

Biosynthesis of the polypeptide chain is realised by a complicated process called translation. The basic polypeptide chain is subsequently chemically modified by the so-called posttranslational modifications. During this sequence of events the peptide chain can be cleaved by directed proteolysis, some of the amino acids can be covalently modified (hydroxylated, dehydrogenated, amidated, etc.) or different so-called prosthetic groups such as haem (haemoproteins), phosphate residues (phosphoproteins), metal ions (metal-loproteins) or (oligo)saccharide chains (glycoproteins) can be attached to the molecule by covalent bonds. Naturally, one protein molecule can be modified by more means. 

A straightforward approach is to hunt for short polypeptides that meet the specificity requirement of an enzyme but which, because of peculiarities of the sequence, are acted upon very slowly. Such a peptide may contain unusual or chemically modified amino acids. For example, the peptide Thr-Pro-nVal-NMeLeu-Tyr-Thr (nVal=norvaline NMeLeu = N-methylleucine) is a very slow elastase substrate whose binding can be studied by X-ray diffraction and NMR spectroscopy.6 Thiol proteases are inhibited by succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide, which includes a sequence common to a number of naturally occurring peptide inhibitors called cystatins.f They are found in various animal tissues where they inhibit cysteine proteases. 

Presumably, a polypeptide ligand modified near the region which binds to the receptor will be inactivated as most of the bifunctional reagents (Table 5.1) are bulky, and on chemical attachment they often neutralize... 

Most polypeptides synthesized on ribosomes are later chemically modified. Thus the formyl group on the N-terminal methionine in polypeptides of bacteria is removed by a deformylase. In both bacteria and eukaryotes, the N-terminal methionine, sometimes along with a few additional amino acids, is removed by aminopeptidases. 

Rs. rubrum, with its single antenna complex, is an ideal object to probe the membrane-surface exposed regions of the antenna polypeptides. Chromatophores (inside-out vesicles, the cytoplasmic side of the membrane outside) have been chemically modified with the hydrophilic marker diazobenzenesulfonate [24], In addition, protease treatment of chromatophores [25-27] and of spheroplasts (periplasm outside) was carried out [27]. The surface location of the B880 complex was further investigated with antibodies raised to either the intact complex or to the individual polypeptides [27]. In addition, the secondary structures of the polypep-... 

Nonstandard amino acids consist of amino acid residues that have been chemically modified after they have been incorporated into a polypeptide or amino acids that occur in living organisms but are not found in proteins. 

Some cells have been observed to change the coding properties of newly synthesized mRNA molecules. In this process, called RNA editing, certain bases are chemically modified, deleted, or added. For example, the mRNA for apolipoprotein B-100 in liver cells codes for a 4563 amino acid polypeptide which is a component of very low density lipoprotein (VLDL). Intestinal cells produce a shorter version of the molecule called apolipoprotein B-48 (2153 amino acid residues) that becomes incorporated into the chylomicron particles produced by these cells. The cytosine in a CAA codon that specifies glutamine is converted by a deamination reaction into a uracil. The new codon, UAA, is a stop signal in translation hence a truncated polypeptide is produced during translation of the edited mRNA. 

Thiolated polymers, also termed thiomers, are conventional mucoadhesive polymers chemically modified to contain a cysteine residue in the polymer chain and thus establish covalent disulfide bonds with mucin." They can be manufactured to be either cationic (mostly thiolated chitosans) or anionic (carboxylic acid-containing polymers) however, their mucoadhesive extent will mostly be determined by their capacity to covalently bind to mucin. The polypeptide backbone of mucin can be divided into three major subunits tandem repeat array, carboxyl-, and amino-terminal domains. While the amino-terminal domain contains some of the cysteine residues, the carboxyl-terminal domain contains more than 10% of the cysteine residues. These cysteine-rich regions are responsible for forming the large mucin oligomers and ultimately, the groups that allow for the covalent mucoadhesive bond formation with oral mucosal systems." ... 

Maurer PH (1970) Antigenicity of polypeptides (poly-a-amino acids) immunogenicity of chemically modified polymers II. Proc Soc Exp Biol Med 134 663-666 Maurer PH, Gerulat BF, Pinchuck P (1966) Antigenicity of polypeptides (poly-a-amino acids). XIX. Studies with chemically modified polymers. J Immunol 97 306-312 Mayer RL (1954) Group-sensitization to compounds of quinone structure and its biochemical basis role of these substances in cancer. Prog Allergy 4 79-172 Miller EC, Miller JA (1960) A mechanism of o-hydroxylation of aromatic amines in vivo. Biochim Biophys Acta 40 380-382... 

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