Early Studies - Glycine

It has been known for many years that the rate of hydrolysis of a-amino acid esters is enhanced by a variety of metal ions such as copper(II), nickel(II), magnesium(H), manganese(II), cobalt(II) and zinc(II).338 Early studies showed that glycine ester hydrolysis can be promoted by a tridentate copper(II) complex coupled by coordination of the amino group and hydrolysis by external hydroxide ion (Scheme 88).339 Also, bis(salicylaldehyde)copper(II) promotes terminal hydrolysis of the tripeptide glycylglycylglycine (equation 73).340 In this case the iV-terminal dipeptide fragment... 

X-ray crystal structure analysis of the amino acid glycine [63], and later confirmed by a neutron diffraction study [65]. The hydrogen-bond lengths and angles are given in Ihble 8.1, together with some other early studies based on neutron diffraction data. 

Early studies on metal-peptide complexes were generally concerned with polyglycines, and there are several reviews on these complexes. In the first part of this article, we will discuss various metal-peptide complexes that have coordinating side chains. Comparison of these metal-peptide complexes will be made with their glycine analogs, and the differences will be noted. The second part of the article will deal with metal-mediated peptide-bond cleavage. 

Early studies on monolayers of chiral molecules like 2-hydroxyalkanes, amphiphilic amino acids, 2-methylhexacosanoic acid esters, and hydroxy-hexadecanoic acid and its esters have been reviewed. The interesting question about monolayers of chiral molecules is whether the parameters which can be determined and the phase transitions are different for pure enantiomers and racemates. For components of biomembranes like phosphatidylcholines 10 this appears not to be the case," but for synthetic compounds like iV-(a-methylbenzyl-stearamide) 11 specific interactions between the molecules of the enantiomers are observed (Chart 2). ° In recent years, advanced techniques have been developed to probe the order in monolayers at the air-water interface, including surface X-ray diffraction, and microscopic techniques, viz. fluorescence microscopy, and Brewster angle microscopy (BAM). The X-ray diffraction technique has been used to identify homochiral and heterochiral two-dimensional domains in mono-layers of racemic amphiphilic amino acids on subphases containing glycine. Fluorescence microscopy requires the introduction in the monolayer of a small... 

Early studies performed with bovine plasma and porcine kidney amine oxidases have shown that the enzymes undergo irreversible inactivation upon reaction with several acetylenic substrates (propargylamine, 2-chloroallylamine and 2-butyne-1,4-diamine), which was diminished by substrate protection [118]. Other types of mechanism-based inactivators of bovine plasma amine oxidase are some glycine esters with relatively acidic a-protons. These esters are converted to ketenes, which may acylate the active site and inactivate the enzyme [119]. 

A third family of hard keratin proteins has been recognized by Gillespie [202]. In early studies, these proteins coprecipitated with low-sulfur proteins [203,204] but were found to represent a distinct family of proteins rich in aromatic residues (tyrosine and phenylalanine), glycine, and serine. These so-called high-tyrosine proteins consisted of two distinct classes, and their proportions varied widely in mammalian keratins (1-30% of total extracts) [205]. Apparently, high-tyrosine proteins are absent in human hair [191]. 

Early studies on the composition of cholestanol-induced gallstones established that they did not contain appreciable amounts of sterol (cholesterol or cholestanol) or pigment but consisted largely of glycine-conjugated bile salts (130,133,139,140). Mosbach and Bevans (139), utilizing cholestanol-14C, demonstrated that approximately half of the bile acids in the stones were... 

The effect of 6-mercaptopurine on the incorporation of a number of C-labelled compounds into soluble purine nucleotides and into RNA and DNA has been studied in leukemia L1210, Ehrlich ascites carcinoma, and solid sarcoma 180. At a level of 6-mercaptopurine that markedly inhibited the incorporation of formate and glycine, the utilization of adenine or 2-aminoadenine was not affected. There was no inhibition of the incorporation of 5(or 4)-aminoimidazole-4(5)-carboxamide (AIC) into adenine derivatives and no marked or consistent inhibition of its incorporation into guanine derivatives. The conversion of AIC to purines in ascites cells was not inhibited at levels of 6-mercaptopurine 8-20 times those that produced 50 per cent or greater inhibition of de novo synthesis [292]. Furthermore, AIC reverses the inhibition of growth of S180 cells (AH/5) in culture by 6-mercaptopurine [293]. These results suggest that in all these systems, in vitro and in vivo, the principal site at which 6-mercaptopurine inhibits nucleic acid biosynthesis is prior to the formation of AIC, and that the interconversion of purine ribonucleotides (see below) is not the primary site of action [292]. Presumably, this early step is the conversion of PRPP to 5-phosphoribosylamine inhibited allosterically by 6-mercaptopurine ribonucleotide (feedback inhibition is not observed in cells that cannot convert 6-mercaptopurine to its ribonucleotide [244]. 

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