Synthesis and cytotoxic activity of new peptides containing basic amino acid residues.

In search of more potent compounds endowed with a cytotoxic activity, a new series of basic peptides was synthesized using solid-phase methods. All peptides were purified by preparative reverse-phase HPLC and characterized by electrospray mass spectrometry. The cytotoxic activity was determined in cultured HeLa cells. The hexadecapeptides 5 and 6 showed a 50% inhibition at the concentration of 30 micrograms/ml. The salmina and the polyamino acids of L-arginine, L-histidine and L-lysine, containing sixteen residues, were virtually inactive. This demonstrates that a specific peptide sequence is necessary to obtain a positive response in HeLa test.

Enhancement of cytotoxic activity by synthesis of peptide multimeric forms.

Synthesis of four multimeric H-Lys-His-His-Arg-Lys-Lys-His-Arg-Lys-Arg-Lys-His-His-Lys-Arg-Lys-oH peptides containing two, four, eight and sixteen branches was carried out by solid phase utilizing a lysine core matrix. These multimeric peptides enhanced activity by inhibiting the colony-forming ability of HeLa cells, from twenty-four to fifty-six times in comparison with the monomeric form. Unexpectedly the peptide with only two-branched sequences showed the highest inhibitory activity.

Synthesis and cytotoxic activity of peptides containing basic amino acids residues.

We synthesized eight peptides containing from three to twenty residues of arginine, lysine and histidine, using an automated synthetiser and Fmoc strategy. All peptides were purified by preparative reverse-phase HPLC and characterized by electrospay mass spectometry. Cytotoxic activity was assessed on HeLa cells. One peptide inhibited the colony-forming ability of tumor cells.

Synthesis of peptide-immunogens corresponding to amino acid sequences from human histocompatibility class II membrane glycoproteins.

Six peptides with amino acid sequences of human histocompatibility Class II membrane glycoproteins were synthesized by conventional solution methods. Five peptides were prepared by stepwise procedures from the carboxyterminus. The sixth was synthesized by fragment condensation (5 + 10 coupling). Antibodies to synthetic peptides were then used to locate exposed and buried regions in the membrane glycoproteins.

Purification, sequence determination and synthesis of seminal plasma peptides and synthesis of some of their analogues.

Three peptides were isolated from bovine seminal plasma and purified to homogeneity. The amino acid sequences, as determined by FAB mass spectrometry, are the following: pGlu-Ala-Glu-Ser-Asn-OH, pGlu-Ala-Glu-Ser(PO3H2-Asn-OH and pGlu-Val-Gly-Glu-Ser-Glu-Asn-OH. These three peptides and some of their analogues were synthesized using liquid- and solid-phase techniques. The pentapeptide pGlu-Ala-Glu- Ser-Asn-OH showed a remarkable affinity for kinase NII and a strong inhibiting activity in DNA transcription. These findings support the hypothesis that phosphorylated acidic domains of nuclear non-histone proteins could bind to DNA, thereby controlling transcription.