Peptides protected

The p nitrophenol formed as a byproduct in this reaction is easily removed by extrac tion with dilute aqueous base Unlike free ammo acids and peptides protected peptides are not zwitteriomc and are more soluble m organic solvents than m water... 

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. 

The thiation procedure described here is an example of a general synthetic method for the conversion of carbonyl to thiocarbonyl groups. Similar transformations have been carried out with ketones, carboxamides,esters,thioesters, 1 actones, " thiol actones, - imides, enaminones, and protected peptides. ... 

In the case of protected peptides, it is necessary to remove the protecting groups by spraying the chromatograms with cone, hydrochloric acid and then heating (20 min, 110°C), before applying the reagent [1]. 

Since the use of N,iV-dimethylacetamide and triethylamine improved the rate and extent of cleavage of the JV-benzyloxycarbonyl group in several difficult cases, these additives have been incorporated into the submitters standard procedure and are included in the present procedures. Deprotection with this method has been carried out with as much as 25 g. of the protected peptide. 

A similar sequence of 12- and 10-membered turns is present in the structure of Boc-protected /S //S -peptides 96 and 97, the C=0 of the Boc group being engaged in the first 12-membered ring with NH of residue 3. The pattern of 10- and 12-membered turns is reversed for the fully protected / // -peptide 94 as well as the unprotected /S //S -dodecapeptide 98 which thus folds into a 10/12-helix, with the NH of residues 1 and 2, respectively being involved in the formation of an N-ter-minal 10-membered turn. 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

Allylic hydroxycrotyl-oligoethylene glyco-n-alkanoyl (HYCRON) linker 25 was applied to the synthesis of protected peptides and glycopep-tides [31]. HYCRON is stable to both acidic and basic conditions and is compatible with Boc- and Fmoc-based chemistry. The preparation of this novel linker is only two steps from commercially available materials. H YCRON linker can be cleaved under neutral conditions using Pd catalyst (Scheme 9). 

Wang SS. p-Alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonylhy-drazide resin for solid-phase synthesis of protected peptide fragments. J Am Chem Soc 1973 95 1328-1333. 

Rink H. Solid-phase synthesis of protected peptide fragments using a trialkoxy diphenyl methylester resin. Tetrahedron Lett 1987 28 3787-3790. 

Albericio F, Barany G. Hypersensitive acid-labile (HAL) tris(alkoxy)benzyl ester anchoring for solid-phase synthesis of protected peptide segments. Tetrahedron Lett 1991 32 1015-1018. 

Rich DH, Gurwara SK. Preparation of a new o-nitrobenzyl resin for solid-phase synthesis of tert-butyloxycarbonyl-protected peptide acids. J Am Chem Soc 1975 97 1575-1579. 

Seitz O, Kunz H. HYCRON, an allylic anchor for high-efficiency solid phase synthesis of protected peptides and glycopeptides. J Org Chem 1997 62 813-826. 

Meisenbach M, Echner H, Voelter W. New methoxy-substituted 9-phenyl-xanthen-9-ylamine linkers for the solid phase phase synthesis of protected peptide amides. Chem Commun (Cambridge) 1997 849-850. 

An analogous synthesis of Z-protected peptide esters is described in reference [47]. The reaction conditions were heating for several hours in anhydrous xylene at 140 °C. 

FORMING REACTIONS TO THE COUPLING OF N-PROTECTED PEPTIDES IS DICTATED BY THE REQUIREMENT TO AVOID EPIMERIZATION 5(4H)-OXAZOLONES FROM ACTIVATED PEPTIDES... 

Activated esters (see Section 2.9) Activated esters of peptides are rarely used because there is no general method available for converting an (V -protected peptide into the ester with a guarantee that it will be a single isomer. Attempts have been made to overcome this obstacle (see Section 7.8). However, solid phase synthesis allows the preparation of thioesters of segments (see Section 7.10). Once the ester is in hand, it can be aminolyzed without generation of a second isomer if suitable conditions are employed. 

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