Peptides, modification

A wide variety of a-tnfluoromethyl a-amino acids are readily available from the reaction of 5-fluoro-4-tnfluoromethyl-l,3 azoles with allylic alcohols [138, 139] a-Tnfluoromethyl-subsumted a-amino acids show anubactenal and antihy pertensive activity Some are highly specific enzyme inhibitors (suicide inhibitors) and may be important as bioregulators [140] Furthermore, they are interesting candidates for peptide modification... 

Toews J, Rogalski JC, Clark TJ, et al. Mass spectrometric identification of formaldehyde-induced peptide modifications under in vivo protein cross-linking conditions. Anal. Chim. Acta. 2008 618 168-183. 

Peptide modification of liposomes offers the potential for enhancing the packaging process and for enhancing each stage of the lipofection process, to ultimately improve transfection efficiency. 

Peptide modification of liposomes has been found to enhance gene transfer up to a 1000-fold (150). They have potential as an equally active and yet safer alternatives to the viral vectors. 

B. Koksch, N. Seewaid, K. Burger, H.D. Jakubke, Peptide modification by incorporation of a-trifiuoromethyi substituted amino acids, Amino Acids 11(3-4) (1996) 425- 34. 

Figure 4.6. Modulation of peptide conformational equilibrium can be achieved through systematic modifications of peptide sequences that direct receptor interactions toward therapeutic response, and away from untoward effects. A systematic peptide modification may lead to reduced concentrations of peptide conformations susceptible to metabolizing enzymes such as peptidases.

Swiderek, K. M. Davis, M. T. Lee,T. D. 1998. The identification of peptide modifications derived from gel-separated proteins using electrospray triple quadrupole and ion trap analyses. Electrophoresis, 19,989-997. 

The 1,1-diaminoalkane derivatives such as 113, developed as a new class of sweet peptides by Goodman et al. 238) on the basis of the retro-inverso peptide modification 20), are 800-1000 times as sweet as sucrose. 

Galonic DP, Ide ND, van der Donk WA, Gin DY. Aziridine-2-carboxylic acid-containing peptides application to solution- and solid-phase convergent site-selective peptide modification. J. Am. Chem. Soc. 2005 127 7359-7369. 

Peptide Modification lodination was carried out on a stainless steel probe target by adding 0.1 % aq. I2 (1 pi) to the dried peptide (ca. 1 pmol). The reaction was stopped after 1 minute by addition of ascorbic acid and the MALDI matrix, a-cyano cinnamic acid in excess. Esterification with ethanol was carried out using the method of Hunt et al. (15), where an acetylchloride and ethanol solution (1 6, v v) was added (5 pi) to the peptide dried in a microcentrifuge tube (ca. 1 pmol). After incubation for 15 minutes at room temperature a 2 mM p-mercaptoethanol (in ethanol) solution was added (1 pi) and the mixture was dried. The matrix, a-cyano-4-hydroxycinnamic acid (2 pi), was added to the micro tube and after 5 minutes 1 pi of this matrix was removed and applied to a target. 

Peptide modification is an essential, yet flexible, synthetic concept for the efficient target screening and optimization of lead structures in the application of naturally occurring peptides as pharmaceuticals. The introduction of side chains directly to a peptide backbone represents a powerful method for the preparation of unnatural peptides [44]. 

Olsen, J.V., Macek, B., Lange, O., Makarov, A., Horning, S., and Mann, M. (2007). Higher-energy C-trap dissociation for peptide modification analysis, Nature Methods, 4,709-712. 

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