Amino Acids, Peptides and Proteins: Volume 29 / Edition 1

by G C Barrett, Don T Elmore, Jenny A Littlechild, Anand S Dutta, Imre Sovago

Overview

In an ever-increasing domain of activity Amino Acids Peptides and Proteins provides an annual compilation of the world's research effort into this important area of biological chemistry. Volume 29 provides a review of literature published during 1996. Comprising a comprehensive review of significant developments at this biology/chemistry interface each volume opens with an overview of amino acids and their applications. Work on peptides is reviewed over several chapters ranging from current trends in their synthesis and conformational and structural analysis to peptidomimetics and the discovery of peptide-related molecules in nature. The application of advanced techniques in structural elucidation is incorporated into all chapters whilst periodic chapters on metal complexes of amino acids, peptides and beta-lactams extend the scope of coverage. Efficient searching of specialist topics is facilitated by the sub-division of chapters into discrete subject areas allowing annual trends to be monitored. All researchers in the pharmaceutical and allied industries and at the biology/chemistry interface in academia will find this an indispensable reference source.

Product Details

ISBN-13:	9780854042173
Publisher:	RSC
Publication date:	10/29/1998
Series:	ISSN , #29
Edition description:	Edition. ed.
Pages:	438
Product dimensions:	5.43(w) x 8.50(h) x (d)

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Amino Acids, Peptides, and Proteins Volume 29

A Review of the Literature Published during 1998

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By J.S. Davies

The Royal Society of Chemistry

Copyright © 1997 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-1-84755-274-7

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CHAPTER 1

Amino Acids

BY GRAHAM C. BARRETT

Introduction

The literature of 1996 is covered in this Chapter, which aims to report and appraise newly-published knowledge of the chemistry of amino acids. Biological aspects are given prominence only where the chemical interest is enhanced by explaining the life science context.

Literature citations forming the basis for this Chapter have been obtained from Chemical Abstracts (Volume 124, Issue no. 11 to Volume 126, Issue no. 9 inclusive), and from papers consulted in major Journals that have consistently been used by authors of relevant material.

The expanding volume of the relevant literature continues to demand ingenuity in somehow getting a litre of wholesome nourishment into the half-litre pot that this Chapter represents, and restrictions have been placed on citations of the patent literature and material of a more routine nature. Authors who repeat-publish and over-fragment their material are responsible to a significant extent for the ever-increasing number of references for this Chapter, and this Reviewer's conscience rests easily when grouping such papers together without detailed comment on each of them.

As usual, the carboxylic acid grouping is understood to be implied by the term 'amino acid' for the purposes of this Chapter, though interest in boron and phosphorus oxy-acid analogues and also in sulfonic acid analogues, is continuing to grow. Methods applicable for the synthesis of α-aminoalkaneboronic acids (Refs. 65, 146, 147), α-aminoalkanesulfonic acids (Refs. 154, 845), and α-aminoalkanephosphonic acids and other phosphorus oxyacids (Refs. 32, 62, 80, 82, 85, 87, 88, 152, 326, 374, 437, 843) are usually derived from extensions of standard methods in the amino acid field, and representative examples of syntheses of amino oxyacid analogues are described, side-by-side with corresponding methods for amino carboxylic acids, in appropriate locations in this Chapter.

2 Textbooks and Reviews

References collected in this Section do not represent the total coverage for this year, since many reviews are located with their primary literature in appropriate sections in this Chapter.

Books on protein analysis and peptide topics inevitably relate to amino acids as well. 1 New books2 and Conference Proceedings are a continuing support for all those working in this flourishing field, and are especially useful to those entering it for the first time and depending on a general background in organic and biological chemistry. Material presented at Conferences is usually published elsewhere, or is already on its way to the primary literature by the time that the Proceedings Volumes appear, and studies covered in this Chapter are linked only to their journal sources even if accessible also through Conference Proceedings.

Reviews cover the twenty-first amino acid utilized in normal ribosome-mediated protein synthesis, selenocysteine (see also the report on incorporation into proteins by modified E.coli of numerous non-natural amino acids), uses of tert-leucine and trans-4-hydroxy-L-proline as chiral starting materials for organic synthesis,(S)-2,3-diaminopropanoic acid, lipidic α-amino acids, che-mical modification of amino acid side-chains for studies of protein function, the detection of amino acids in samples collected on Mars, naturally-occurring praline analogues, analysis methods for D-α-amino acids and discussion of their in vivo roles, free-radical reactions in the synthesis of amino acids, cation π-binding between aromatic amino acid side-chains in host-guest complexes, synthesis and uses of α-trifluoromethyl-α-amino acids, and L-carnitine biochemistry. As with earlier issues of the 'Methods in Molecular Biology' series, useful material on amino acids science is contained in current Volumes, and the same applies to American Chemical Society Symposia.

3 Naturally Occurring Amino Acids

3.1 Isolation of Amino Acids from Natural Sources – New solutions to problems of winning of amino acids from mixtures, by conventional or novel methods are collected in this Section. Protein hydrolysis is important both in terms of reliability of analytical data, and as a source of certain amino acids on a preparative scale. The recovery of tryptophan (86–88%) from seaweed is considerably better by aqueous alkaline hydrolysis than by mercaptoethanesulfonic acid degradation (though the latter method is claimed to give >90% recovery of tryptophan from proteins when dithioglycollic acid is added. Degradation accompanying conventional acid hydrolysis of a protein is even greater for cysteic acid than for serine. A new enzyme, actinase, that catalyses the hydrolysis at both peptide bonds that anchor a tyrosine residue within a protein, may be widely useful; for example, the tyrosine content (12%) is released from silk through its action.

Further details (see Vol. 28, p. 3) of the application of an emulsion liquid membrane consisting of di-(2-ethylhexyl)phosphoric acid, Span 80, and kerosene, for concentrating alanine from aqueous solutions, have been published. An organic membrane has been formulated for the separation by nanofiltration of arginine, glutamic acid, and serine from an aqueous solution containing 15 amino acids, and N-benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester hydrochloride can be concentrated and separated from each other in solutions in organic solvents, by using reverse osmosis membranes. N-Acylation of protein hydrolysates has been claimed to provide easier separation, though the well-known further reactions undergone by N-acylamino acids and acylating agents may create more confusion. A novel approach, temperature-swing chromatography, has been applied to the preparative scale separation of a mixture of arginine, histidine, and lysine. Conventional large-scale ion-exchange purification methods have concentrated on the removal of inorganic impurities from amino acid mixtures.

An effective solvent system for amino acids and their derivatives is dimethylformamide containing a strong acid (TFA, HBF4, TosOH etc.) together with an excess of tertiary amine with pK less than 6 (pyridine is recommended). Derivatization of amino acids, e.g. by acylation, is claimed to be feasible in such systems, but it should be appreciated that troublesome side-reactions unique to amino acids would be expected for syntheses carried out in such media.

Crystallization techniques leading to pure products are routine final steps in isolations of amino acids from mixtures, and new data are contained in studies of aspartic acid and phenylalanine.

3.2 Occurrence of Known Amino Acids – This section could be very extensive, but it does not include routine papers mentioning familiar amino acids in their predictable locations in the biosphere; therefore, only those papers describing familiar amino acids in unusual locations (extraterrestrial; Ref. 11), or describing more unusual amino acids in natural locations, are considered.

Glycine appears in hydrolysates of bacterial lipopolysaccharides, and is concluded to be an integral constituent. L-Arginine appears in Coccinellidae subcoccinella-24-punctata as its Nα-quinaldyl derivative, and in the marine ascidian Leptoclinides dubius as corresponding p-hydroxybenzoyl and 6-bromo-1H-indolyl-3-carbonyl derivatives; also present are Nα-(1H-indolyl-3-carbonyl)-D-arginine, Nα-(6-bromo-1H-indolyl-3-carbonyl)-L-histidine, and the rare amino acid L-enduracidin. Assignments of structure to konbamidem (from the sea sponge Theonella sp.) and related cyclic peptides are shown to be incorrect by synthesis of tryptophan-containing analogues of the proposed peptides, and creation of D- and L-2-bromo-5-hydroxytryptophan residues by NBS bromination. Hypusine Nε (4-amino-2-hydroxybutyl)-L-lysine] is formed by transfer of the side-chainsubstituent from spermidine to a lysine residue in a protein.

The opines [α-(N-carboxyalkylamino)alkanoic acids; ten such compounds are uniquely located in 43 crown gall tumours] have been surveyed. N ε-Carbox- ymethyl-L-lysine is an advanced glycation end-product of proteins in vivo, and is thought to arise by reaction with compounds formed by lipid peroxidation since it can be generated in vitro by copper-catalysed oxidation of mixtures of proteins with polyunsaturated fatty acids. Crosslinking amino acids released from proteins in vivo, that then find their way into clinical samples, are attracting increasing interest since they are thought to be markers of human bodily deterioration; deoxypyridinoline is one of these (a marker for osteoporosis; see also Refs.1048,1075-1078) and its identification in urine together with hydroxyproline has been studied.

Biosynthesis by Streptomycetes of 3-amino-5-hydroxybenzoic acid involves a new variant of the shikimate pathway, since 3, 4-dideoxy-4-aminoarabinoheptulosonic acid, 5-deoxy-5-amino-3-dehydroquinic acid (aminoDHQ, I) and 5-deoxy-5-amino-3-dehydroshikimic acid (2) are present in cultures. Pyridazomycin (3) is biosynthesized from ornithine, glycine, and a C-4 unit. The antimetabolite YS-460 from a Streptomyces sp. turns out to be identical with furanomycin. Nostocyclin, from newly-discovered Nostoc strains, extends the list of cyclodepsipeptides of cyanobacteria (blue-green algae) that contain the 3-amino-6-hydroxy-2-piperidone moiety.

3.3 New Naturally Occurring Amino – Acids Neocosmospora vasinfecta contains (2S,3R,4R,6E) -2-acetylamino-3-hydroxy-4-methyloct-6-enoic acid (structure assigned on the basis of synthesis by aldolization of tert-butyl isocyanoacetate and routine elaboration; Section 4.2).

3.4 New Amino Acids from Hydrolysates – This section covers new amino acids that occur as residues in larger structures that can in principle be broken down by hydrolysis.

The most prolific growth area under this heading is the group of cyclic dipeptides (alias dioxopiperazines), and new examples include diatretol (4; from Clitocybe diatreta) and the four cyclotryprostatins (5) from Aspergillus fumigatus BM 939 that are responsible for inhibition of cell cycle progression.

Studies of the fluorescent 'crossline', a lysine residue in proteins that has become post-translationally modified through condensation with D-glucose, have been reported. A di-isotyrosine isolated from hydrolysates of cell walls of tomato cell cultures has been shown to be a biphenyl rather than a diaryl ether.

Of course, the field covered by this section includes acylated amino acids as well as unusual peptides and crosslinked proteins. The first-mentioned of these classes is represented in the modulators of the proliferation of mammalian cells, the sparoxomycins A1 and A2 (6; these are epimers at the sulfoxide chiral centre). The trypsin inhibitor radiosumin (7), from the blue-green alga Plectonema radiosum, contains unsaturated moieties that are novel in the amino acid context, while clathramides A and B (8) are novel bromopyrroles from the sponge Agelas clathrodes. The chymotrypsin inhibitor oscillatorin (from the toxic freshwater cyanobacterium Oscillatoria agardhiz) is a cyclic decapeptide that contains 3a-cis-1,2,3,3a,8,8a-hexahydro-3a-(3-methyl-2-butenyl)-pyrrolo[2, 3-b]-indole 2-carboxylic acid (9). Progress with the structure determination of kedarcidin has been reported; its incompletely defined chromophore contains partial structure (10).

The novel amino acid (11) is released from pheomelanins through alkaline hydrogen peroxide treatment at room temperature.

4 Chemical Synthesis and Resolution of Amino Acids

4.1 General Methods for the Synthesis of ex-Amino Acids – Routine methods based on the amination of carbonyl compounds, carboxylation of amines, and alkylation of glycine derivatives continue to provide the main material under this heading.

Significant modifications providing improvements to standard methods are noticeable, and over the years there have been continuous developments, including improved deprotection conditions [alkaline hydrolysis of N-phthaloyl-glycine and acid hydrolysis of N-(o-carboxybenzoyl)glycine in aqueous organic solvents] for the Gabriel synthesis. Attempted aminolysis of dimethyl 1-bromocyclopropane-1,2-dicarboxylate in methanol gave the methyl ether. Amination through azidolysis of α-halogenonitriles followed by reduction of the azide grouping and hydrolysis of the nitrile is another standard approach, illustrated in this year's literature with 1-halogeno-D-tetra-O-acetylglycopyranosyl cyanides giving monosaccharides carrying amino and carboxy groups at the anomeric carbon. Azidolysis of cyclic carbonates (using NaN3) or oxiranes (using 1,1,3,3-tetramethylguanidinium azide with a simple transition-metal salt as catalyst) en route to trans-1,2-amino alcohols (see also Refs. 125, 128 etc.) is the first step in an easy introduction of a primary amine function. Reductive addition of hydrazoic acid to γ-keto-α,β-unsaturated dicarbonyl compounds, e.g. lactones (12), offers an alternative approach to this amination protocol. Lithiated cycloalkanephosphonate esters and N-acylmethylanilides have undergone electrophilic azidation (diphenyl phosphorazidate) followed by reduction (H2/Pd) and hydrolysis, to lead to α-aminoalkanephosphonic acids and α-amino acids, respectively.

Vinylglycinol has been obtained by Pd(naphthalene)-catalysed amination of butadiene mono-epoxide by phthalimide. α-N-Boc-Aminoalkaneboronate esters have been obtained through amination (BocNHNa) of α-halogenoalkane-boronates.

Nitrosation of β-ketoesters (Scheme 1) giving α-oximino-esters, and electro- philic amination of the corresponding α-hydroxy ester with di-tert-butyl azodi-carboxylate to give the α-hydrazino β-hydroxy ester, are the initial steps for two standard amination protocols used for the syntheses of the vancomycin constituents, syn- and anti-β-hydroxy 3-chlorotyrosines, respectively. β-Alkoxy-α-oximino-esters have been prepared from oxiranes and hydroxylamine, and easily-prepared α-oximinoalkanephosphonates are readily reduced (NaBH4) to α-aminoalkanephosphonates.

Another 'named' method also based on amination, the Strecker synthesis, has been used with carbonyl compounds derived from protected D-glyceraldehydes to give (2S,3S)- and (2R,3S)-2-amino-3, 4-dihydroxybutanoic acids; the Strecker synthesis gives poor yields when attempting the synthesis of amino acids bearing electron-withdrawing groups such as 4-pyridyl. A close relative of the method is involved in a synthesis of phenylglycine from benzaldehyde, CHC13,, KOH and ammonia; an identical brew has been studied over many years and this time inclusion of β-cyclodextrin in the reaction mixture is shown to generate stereo-selectivity (to an extent that is not clear from information in the abstract).

Ugi solid-phase syntheses, one (employing 1-isocyanocyclohexene) giving α-amino acid derivatives via a munchnone intermediate, and a related approach giving hydantoin-4-imides in another way (the isocyanide is tethered to the solid phase), have been studied. These are being studied in the context of the generation of combinatorial compound libraries, as is a route to 5-alkoxyhydantoins employing α-hydroxyalkanoylated Merrifield resin (BnONH2 followed by ArNCO). The rich reactivity profile of the munchnone intermediate involved in these studies can be exploited in other ways, e.g. 1,3-dipolar cycloadditions with alkynes leading to pyrroles (see also Ref. 72).

A '5-centre-4-component reaction' (aldehyde, L-amino acid, isocyanide, and alkanol) leads to homochiral 1,1'-iminodicarboxylic acid derivatives. Reactions of chiral imino aziridines (the synthetic equivalent of the condensation of three of the four components of the classical Ugi reaction) with alkanoic acids give N-acylamino acid amides with very little racemization, as well as analogues resulting from Mumm rearrangement. Optically-active zirconaziridines (13) can be trapped with ethylene carbonate (a 'CO2 synthon') as they are formed, and the resulting complex generates α-amino-α-methyl esters, or gives phenylglycinamides when isocyanates are added; optically-active substrates generate poor enantios-electivity.

Amination of keto-acids leading to α-aminoalkylphosphonic acids has been demonstrated, employing benzhydrylamine and reduction of the resulting Schiff base with K(OAc)3BH; a synthesis of phosphohomoserine lactone is included. Amination of azadienes through cycloaddition to arylnitroso compounds (Scheme 2) gives N-arylamino acids through reductive cleavage. Mitsunobu amination of α-hydroxyphosphonates formed from dibenzyl phosphite and aldehydes is an effective route to N-hydroxy-α-aminophosphonates.

(Continues...)

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Excerpted from Amino Acids, Peptides, and Proteins Volume 29 by J.S. Davies. Copyright © 1997 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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Table of Contents

Contents

Chapter 1 Amino Acids By Graham C. Barrett, 1,
Chapter 2 Peptide Synthesis By Don T. Elmore, 126,
Chapter 3 Analogue and Conformational Studies on Peptide Hormones and Other Biologically Active Peptides By A.S. Dutta, 175,
Chapter 4 Cyclic, Modified and Conjugated Peptides By J. S. Davies, 262,
Chapter 5 Metal Complexes of Amino Acids and Peptides By E. Farkas and I. Sóvágó, 324,
Chapter 6 Current Trends in Protein Research By Jennifer A. Littlechild, 387,