Solid phase fragment condensation

Another solid phase fragment condensation with CDI and 1-hydroxybenzotriazole in the synthesis of the human insulin B-chain afforded the oligopeptide in 75% yield. The reaction time with the coupling pair CDI/HOBt was shorter than in the case of the DCC/ HOBt system.136 The CDI/HOBt activation method was also applied to the synthesis of a... 

Benz, H. The Role of Solid-Phase Fragment Condensation (SPFC) in Peptide Synthesis, Synthesis 1994,4, 337. 

R. B. MelTifleld, Solid phase peptide synthesis. I. The synthesis of a tetrapeptide, J. Am. Chem. Soc. 85 2149 (1963) for recent reviews see (a) H. Benz, The role of solid-phase fragment condensation (SPFC) in peptide synthesis, Synthesis p. 337 (1994) (b) P. Lloyd-Williams, F. Alberico, and E. Giralt, Convergent solid phase peptide synthesis. Tetrahedron 49 11065 (1993). 

Synthesis of the peptide Ac-A-Bn-C-OH was performed by a stepwise solid-phase fragment condensation approach, as shown in Scheme 3, using the general procedures of the automated solid-phase method. The synthesis began with Boc-C-resin support and continued with the stepwise addition of protected peptide fragments until the completed peptide was assembled on the resin. The supported peptide Ac-A-Bn-C-resin was obtained after deprotection of Boc-A-Bn-C-resin and acetylation of the free amino groups. 

Stepwise Solid-Phase Fragment Condensation General Procedure 21 ... 

We chose to study the efficiency of the solid phase fragment condensation on the example of a type III antifreeze-protein (64 amino acids, 6.7 KDa), isolated... 

Figures. Fmoc-ProTa(87-94)-OH and the resin-bound ProTa(95-109) used for the evaluation of racemization suppressing conditions in solid phase fragment condensation.

It has long been recognized that fragment condensation on a solid phase would be highly desirable. 1,5,6 However, the solid-phase fragment coupling approach has been limited by the notoriously poor solubility properties of fully protected peptides that make them difficult to purify and characterize. 

An alternative to the synthesis of proteins by classical fragment synthesis in solution or by solid-phase synthesis on a support is the use of enzyme-catalyzed condensation of amino acids or peptides. This possibility was first demonstrated in 1938 91 with the synthesis of poorly soluble benzoyl-leucyl-leucine anilide by papain catalysis. After many years, this approach was extended to the preparation of peptide hormones such as Leu-enkephalin 92 and dynorphin(l -8).[93 This was made possible by the use of highly purified enzymes and by careful control of reaction conditions. The basic principles of protease-catalyzed peptide bond formation have been discussed.194 ... 

Celovsky, V. and Bordusa, F. (2000). Protease-catalyzed fragment condensation via substrate mimetic strategy a useful combination of solid-phase peptide synthesis with enzymatic methods. /. Pept. Res., 55, 325-9. 

The syntheses of only a very few (A-aminoamide) peptides, with no examples of solid-phase synthesis, have been reported in the literature. The low yield in -coupling calls for the fragment condensation methodology, which has been applied to the synthesis of the HIV protease substrate analogues 79 and 80 (Scheme 23)J50]... 

A distinction must be made between truly isolated molecules which react in the absence of any collision with other molecules, as in the gas phase at very low pressures or in molecular beams, and molecules in liquid or solid environments. A condensed phase medium, liquid or solid, imposes a cage effect which can prevent large geometrical changes in rearrangement reactions, and the separation of fragments in dissociation reactions. 

Scheme 3 Synthesis of Coiled-Coil Analogues of Various Polypeptide Chain Lengths (Ac-ABnC-OH) by Stepwise Solid-Phase Condensation of Protected Heptad Fragments 21111...

Synthesis of octreotide and derivative thereof can be carried out by two methods. The first method is synthesized initially by fragment condensation solution phase procedures. The synthetic process of octreotide has been described by Bauer et al. (1). The second method is the synthese by solid-phase procedures. Edward et al. (2) isolated side chain protected octreotide with a total yield of 14% by cleaving the protected peptide from the resin with threoninol. Arano et al. (3) carried out another solid phase method for octreotide, and produced it in overall 31.8% yield based on the starting Fmoc-Thr(tBu)-ol-resin. The basic difference from the other procedures already described is that the introduction of the threoninol is carried out upon the protected peptidic structure (resin-free), which, when appropriately activated, leads quantitatively and without needing to make temporary protections upon the threoninol, to the protected precursor of octreotide, which in turn, with a simple acid treatment leads to octreotide with very high yields. 

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