Peptide chemistry

These methodologies have been reviewed (22). In both methods, synthesis involves assembly of protected peptide chains, deprotection, purification, and characterization. However, the soHd-phase method, pioneered by Merrifield, dominates the field of peptide chemistry (23). In SPPS, the C-terminal amino acid of the desired peptide is attached to a polymeric soHd support. The addition of amino acids (qv) requires a number of relatively simple steps that are easily automated. Therefore, SPPS contains a number of advantages compared to the solution approach, including fewer solubiUty problems, use of less specialized chemistry, potential for automation, and requirement of relatively less skilled operators (22). Additionally, intermediates are not isolated and purified, and therefore the steps can be carried out more rapidly. Moreover, the SPPS method has been shown to proceed without racemization, whereas in fragment synthesis there is always a potential for racemization. Solution synthesis provides peptides of relatively higher purity however, the addition of hplc methodologies allows for pure peptide products from SPPS as well. 

M. Bodansky, Peptide Synthesis, 2nd ed., John Wiley Sons, Inc., New York, 1976 J. Meinhofer in Ref. 1, Chapt. 9, p. 297 G. R. Pettit, Synthetic Peptides, Vols. 1—4, Van Nostrand Reinhold, New York, 1980, Vols. 5, 6, Elsevier New York, 1982 E. Shroeder and K. Luebke, The Peptide, Vol. 1, Methods of Peptide Synthesis, Academic Press, New York, 1965 N. Izumiya and co-workers. Fundamentals and Experiments of Peptide Synthesis (in Japanese), Mamzen, Tokyo, Japan, 1987 R. B. Merriheld,/ Mm. Chem. Soc. 85, 2149 (1963) G. Barany and R. B. Merriheld in E. Gross andj. Meinenhofer, eds.. The Peptides Mnalysis, Synthesis, Biology, Vol. 2, Academic Press, New York, 1980, pp. 1—284 G. R. Marshall, Peptides Chemistry and Biology, Escom, Leiden, The Netherlands, 1988. 

M. Bodanszky, Principles of Peptide Chemistry, Springer-Verlag, New York, 1984, p. 99. 

Since there are a number of excellent and extensive reviews of peptide chemistry,6-9 no attempt will be made here to describe the known methods of peptide synthesis. Absolute comparisons of the procedure presented herein with other methods of peptide synthesis are impossible... 

This field has also inspired the development of a range of pseudo-peptides, that is polyamides composed of amino acids other than a-amino acids. These include for instance peptoids, /9-amino acid oligomers and also compounds such as peptide nucleic acids and DNA binding polyamides, all of which share the amide (peptide) chemistry with natural peptides. 

In peptide chemistry, the term "pseudopeptide" is commonly used to denote a peptide in which some or all of the amino acids are linked together by bonds other than the conventional peptide Linkage (13). Such pseudopeptides have found applications as specific structural... 

Adamantane can be used to construct peptidic scaffolding and synthesis of artificial proteins. It has been introduced into different types of synthetic peptidic macrocycles, which are useful tools in peptide chemistry and stereochemistry studies and have many other applications as well. Introduction of amino acid-functionalized adamantane to the DNA nanostmctures might lead to construction of DNA-adamantane-amino acid nanostmctures with desirable stiffness and integrity. Diamondoids can be employed to constmct molecular rods, cages, and containers and also for utilization in different methods of self-assembly. In fact, through the development of self-assembly approaches and utilization of diamondoids in these processes, it would be possible to design and constmct novel nanostmctures for effective and specific carriers for each dmg. 

Wakselman, M. Mazaleyrat, J.-P. Lin, R. C. Xie, J. Vigier, B. Vilain, A. C. Fesquet, S. Boggetto, N. Reboud-Ravaux, M. Design, synthesis and study of a selective cyclopeptidic mechanism-based inhibitor of human thrombin. In Peptides Chemistry, Structure... 

Synthesis of Tyrosine Derivatives. Tyrosine derived monomers were prepared by DCC mediated coupling reactions in THF following standard procedures of peptide chemistry (72). Dat-Tym, Z-Tyr-Tym, Z-Tyr-Tyr-Hex, and Dat-Tyr-Hex (DTH) were purified and characterized according to reference 10. For spectral data of Z-Tyr-Tyr-Hex, see Kohn and Langer (75). 

Schiller PW, Nguyen TM-D, Berezowska I, Weltrowska G, Schmidt R, Marsden BJ, Wilkes BC, Lemieux C, Chung NN. The TIPP opioid peptide family development of a new class of highly potent 6-receptor antagonists with extraordinary -selectivity. In Yanaihara N, ed. Peptide Chemistry 1992 (Proceedings of the 2nd Japanese Symposium on Peptide Chemistry. Leiden, The Netherlands Escom Science Publishers, 1993 337-340. 

The triphenylmethyl function, also known as trytil (Trt), is a valuable bulky protecting group for peptide chemistry. Trytil groups confer acid-labile protection onto amines, but effective removal can also be achieved by catalytic hydrogenolysis. 

However, in the presence of COCI2, the amino acids are converted to cyclic anhydrides, which are referred to in peptide chemistry as Leuchs anhydrides . These polymerize in aqueous media to give peptides, without the formation of larger amounts of diketopiperazines (Brack, 1982). 

New developments in chemistry can arise from the planning and testing of new synthetic methods. In contemporary chemistry, we can see developments whose roots can be found in biological processes, as the terms signal recognition , replication , autocatalysis or self-replication indicate. Modern ideas in these areas can be found in laboratories where work on peptide chemistry is being carried out. 

Thioamides and their use in the preparation of the heterocyclic compounds are widely reported in the literature. Also they attract considerable interests in peptide chemistry. Molecular and crystal structures of some thioamide derivatives have been confirmed by X-ray diffraction data.8 10 Lawesson s reagent or phosphorus pentasulfide (P4S10) is actively used for the synthesis of thio-carbonyl compounds. Their preparation methods, reactions, applications in the synthesis of heterocycles and biological effects are mainly described in this section. 

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