Fmoc-D-tyrosine

Four new low molecular weight hydrogelators (LMWGs) have been prepared in multigram scale and their attitude to form hydrogels has been tested. The gelation trigger is pH variation. The resulting gels have been characterized with several techniques: measurement of the melting points (T(gel)), transparency, gelation time, and viscoelastic properties, together with ECD analysis. Among them, Fmoc-L-Tyr-D-Oxd-OH 1 is an excellent gelator that leads to the preparation of strong, transparent, and viscoelastic gels, by pH variation. UV-visible analyses have demonstrated that the gels obtained with the LMWG 1 possess high transparency, with a transmittance up to 25.6% at a wavelength of 600 nm. Results of the amplitude sweep experiments showed that the elastic response component (G') was approximately an order of magnitude larger than the viscous component, indicating an elastic rather than viscous attitude of the gels, confirmed by the frequency independence of G' and G″ values, in the range from 0.

We have been engaged in the microwave-solid phase peptide synthesis (SPPS) synthesis of the phenylglycine (Phg)-containing pentapeptide H-Ala-Val-Pro-Phg-Tyr-NH(2) (1) previously demonstrated to bind to the so-called BIR3 domain of the anti-apoptotic protein XIAP. Analysis of the target peptide by a combination of RP-HPLC, ESI-MS, and NMR revealed the presence of two diastereoisomers arising out of the racemisation of the Phg residue, with the percentage of the LLLDL component assessed as 49%. We performed the synthesis of peptide (1) using different microwave and conventional stepwise SPPS conditions in attempts to reduce the level of racemisation of the Phg residue and to determine at which part of the synthetic cycle the epimerization had occurred. We determined that racemisation occurred mainly during the Fmoc-group removal and, to a much lesser extent, during activation/coupling of the Fmoc-Phg-OH residue. We were able to obtain the desired peptide with a 71% diastereomeric purity (29% LLLDL as impurity) by utilizing microwave-assisted SPPS at 50 °C and power 22 Watts, when the triazine-derived coupling reagent DMTMM-BF(4) was used, together with NMM as an activator base, for the incorporation of this residue and 20% piperidine as an Fmoc-deprotection base.

Template-constrained cyclic sulfopeptides that inhibit HIV-1 entry were rationally designed based on a loop from monoclonal antibody (mAb) 412d. A focused set of sulfopeptides was synthesized using Fmoc-Tyr(SO3DCV)-OH (DCV = 2,2-dichlorovinyl). Three cyclic sulfopeptides that inhibit entry of HIV-1 and complement the activity of known CCR5 antagonists were identified.

Obtaining homogenous aspartyl-containing peptides via Fmoc/tBu chemistry is often an insurmountable obstacle. A generic solution for this issue utilising an optimised side-chain protection strategy that minimises aspartimide formation would therefore be most desirable. To this end, we developed the following new derivatives: Fmoc-Asp(OEpe)-OH (Epe = 3-ethyl-3-pentyl), Fmoc-Asp(OPhp)-OH (Php = 4-n-propyl-4-heptyl) and Fmoc-Asp(OBno)-OH (Bno = 5-n-butyl-5-nonyl). We have compared their effectiveness against that of Fmoc-Asp(OtBu)-OH and Fmoc-Asp(OMpe)-OH in the well-established scorpion toxin II model peptide variants H-Val-Lys-Asp-Asn/Arg-Tyr-Ile-OH by treatments of the peptidyl resins with the Fmoc removal reagents containing piperidine and DBU at both room and elevated temperatures. The new derivatives proved to be extremely effective in minimising aspartimide by-products in each application.