Peptides evaluation

R. T., Acyloxyalkoxy-based cyclic prodrugs of opioid peptides evaluation of their chemical and enzymatic stability as well as their transport properties across Caco-2 cell mono-layers, Pharm. Res., 1999, 36, 24-29. 

G. M. Pauletti, S. Ganwar, B. Wang, R. T. Borchardt, Esterase-Sensitive Cyclic Prodrugs of Peptides Evaluation of a Phenylpropionic Acid Promoiety in a Model Hexapeptide , Pharm. Res. 1997, 14, 11-17. 

Craig, J.A., E.L. Rexeisen, A. Mardilovich, K. Shroff, andE. Kokkoli. 2008. Effect oflinker and spacer on the design of a fibronectin mimetic peptide evaluated via cell studies and AFM adhesion forces. Langmuir 24(18) 10282-10292. 

The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

With its structure known, the synthesis of a peptide can then be undertaken— perhaps to obtain a larger amount for biological evaluation. A simple amide might be formed by treating an amine and a carboxylic acid with dicyclo-hexylcarbodiimide (DCC Section 21.7), but peptide synthesis is a more difficult problem because many different amide bonds must be formed in a specific order rather than at random. 

The accumulated cells do not carry an HIV provirns (Egelhofer et al. 2004). This peptide has been clinically evaluated as described later. 

Fig. 2.9 Geminally disubstituted amino acids synthesized to evaluate the preferential conformations of and -peptides...

Fig. 2.40 Sequences and helical wheel representation of amphiphilic 2.5,2-helical jS-pep-tide 17-mers evaluated for antimicrobial activity [234, 248]. These peptides are exclusively composed of hydrophobic trans-ACPC...

Hongmanee P., Stender H., Rasmussen O.F. Evaluation of a fluorescence in situ hybridization assay for differentiation between tuberculous and nontuberculous Mycobacterium species in smears of Low-enstein-Jensen and mycobacteria growth indicator tube cultures using peptide nucleic acid probes. J. Clin. Microbiol. 2001 39 1032-1035. 

Vasoactive Peptides. More recent studies show a beneficial effect of vasopressin which should be evaluated further in clinical trials [58]. 

Liu B, Lewis AK, Shen W (2009) Physical hydrogels photo-cross-linked from self- assembled macromers for potential use in tissue engineering. Biomacromolecules 10 3182-3187 Vandermeulen GWM, Tziatzios C, Duncan R et al (2005) Peg-based hybrid block copolymers containing alpha-helical coiled coil peptide sequences control of self- assembly and preliminary biological evaluation. Macromolecules 38 761-769... 

Wu YQ, Belyakov S, Chi Choi, Limburg D, Thomas BE IV, Vaal M, Wei L, Wilkinson DE, Holmes A, Fuller M, McCormick J, Connolly M, Moeller T, Steiner J, Hamilton, GS. Synthesis and biological evaluation of non-peptidic cyclophilin ligands. J Med Chem 2003 46 1112-15. 

Fig. 7.1 CXCL12 sequence showing the reported processing by proteases. Highlighted are the sequences involved in CXCR4 binding and activation, and the two peptides, CXCL12(5-19) and CXCL12(20-33), evaluated for their abUity to compete with CXCL12(5-67) in binding to its receptor...

The localisation of a particular peptide to a particular brain area and possibly associated with a particular transmitter (e.g. CCK with dopamine in mesolimbic pathways) has often prompted a prediction of function (e.g. CCK may have a role in schizophrenia). Animal studies in which the peptide has been injected into the appropriate brain area or tested on slices taken from the brain area have sometimes been taken to confirm such hypotheses. These approaches have lined up the peptides for a whole range of potential roles, some of which are listed in Table 12.4. Whether these predictions are realities will depend on the availability of chemical agents and their evaluation, not only in animals but also in humans. 

Clearly many more data are needed on the release of these peptides and their function in GP before their possible role in PD can be properly evaluated but they illustrate an interesting alternative approach to therapy. 

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