Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

Synthesis of triethyl N-formyl-N-phosphonomethylglycinate and diethyl N-formyl-N- phosphonomethylglycine and studies of their rotational conformers by dynamic NMR

Reaction of ethyl N-phosphonomethylglycinate with triethyl orthoformate gave a mixture of triethyl N-formyl-N-phosphonomthylglycinate (3) and diethyl N-formyl-N-phosphonomethylglycine (4), the rotational barriers of which have been investigated theoretically and experimentally

Conformational polymorphism of diethyl 1-(phthalylglycyloxy)-2-phthalylaminoethenephosphonate

In course of the synthesis of phosphonic derivatives of bestatine, several products have been obtained. One of them turned out to occur in two polymorphic forms. Two crystal structures correspond to two molecular conformations. The crystal structures are as follows: (1a) C24H21N2O9P, P2(1)/n, a = 8.023(2) Angstrom, b = 12.092(2) Angstrom, c = 24.103(5) Angstrom, beta = 92.39(3)degrees, Z = 4, (1b) C24H21N2O9P, P2(1)/c, a = 8.322(1) Angstrom, b = 16.378(2) Angstrom, c = 18.442(2) Angstrom, beta = 101.13(1)degrees, Z = 4. The main conformational difference consists in the mutual orientation of two phthalyl rings. The conformation and packing of sterically overcrowded and conformationally flexible molecules seem to be stabilized by very weak C-H...O hydrogen bonds. The extremely large thermal vibration amplitudes of the phosphonic group's atoms indicate the occurrence of disorder, probably of dynamical character. This disorder becomes frozen below room temperature. The differential scanning calorimetry (DSC) revealed the occurrence of phase transitions below room temperature in both crystals. (C) 2001 Elsevier Science B.V. All rights reserved

Peptidomimetic synthesis: drug discovery for Alzheimer's disease

The biomolecular system mainly consists of nucleic acids, proteins, peptides, and sugar chains, and they play a critical role in cell growth, differentiation induction, apoptosis, and immunity. Among these components, peptides are the most commonly studied due to their relatively low molecular weight and high biocompatibility as well as in vitro and in vivo lability and often applied as drugs, agricultural chemicals, food, and tools in diagnostic and biological research. Peptidomimetics have been reported to function as protein-protein interaction inhibitors and thus could serve in many biomolecular systems. This chapter describes the synthesis of peptidomimetics used for discovery of drugs that target β-secretase inhibitors and amyloid-β aggregation inhibitors in Alzheimer's disease. For this purpose, natural amino acids and other synthetic acids or amines were used in a solid-phase peptide synthesis (SPPS)