Biomedical subjects

K Kaljuste

Publications and source records attributed to K Kaljuste.

3 recordsLinked to original sources

PubMed1996

Backbone-to-backbone cyclized and linear pseudopeptide analogs of substance P as ligands to the substance P receptor from rat brain.

Two series of backbone modified substance P analogs were synthesized. In the first group of analogs the N-terminal region of substance P, SP(1-4), was replaced by a polyamine segment or aliphatic omega-amino fatty acid residues. Two of these analogs displaced 125I-Bolton-Hunter labeled substance P from rat brain synaptosomes with IC50 values of 1.3 +/- 0.5 and 1.6 +/- 0.3 nM, respectively. These affinities are similar to that of substance P (IC50 1.3 nM). The second group of analogs were a set of backbone-to-backbone cyclized pseudopeptides. In these analogs two peptide bonds at the C-terminal portion of substance P were replaced by the reduced peptide bonds (psi[CH2NH]) which were further reductively alkylated with 3(4-methylbenzylthio)propanal. After cleavage from the resin the peptides were oxidized into a cyclic disulfide. All of the cyclic analogs of substance P interacted with the NK1 receptor from rat brain with IC50 values in the micromolar range.

Animals↗

PubMed1994

A new general solid-phase method for the synthesis of backbone-to-backbone cyclized peptides.

A model peptide with the sequences Ala-Pro-Lys(2ClZ)-Tyr(2BrZ) was synthesized on a 4-methylbenzhydryl amine (MBHA) polystyrene resin using conventional Boc/benzyl protective group strategy. The amino acid aldehyde Boc-valinal was coupled by reductive alkylation with NaCNBH3 in acidified DMF for 1 h. The secondary amine in the peptide-resin Boc-Val psi[CH2NH]Ala-Pro-Lys(2ClZ)-Tyr(2BrZ)-MBHA was reductively alkylated by 3(4-methylbenzylthio)-propanal at 40 degrees C for 6 h, resulting the peptide-resin Boc-Val psi[CH2N(CH2CH2CH2-S-pMeBzl)]Ala-Pro-Lys(2ClZ)-T yr(2BrZ)-MBHA. After the removal of the Boc group the synthesis was continued employing the above-mentioned methods, which led to the resin-bound peptide Leu psi[CH2N(CH2CH2CH2S-pMeBzl)]Ser-Pro-Gly-Lys(2ClZ )-Val psi [CH2N(CH2CH2CH2-S-pMeBzl)]Ala-Pro-Lys(2ClZ)-Tyr( 2BrZ)-MBHA. The peptide was cleaved from the resin with hydrogen fluoride. Reversed-phase HPLC and plasma desorbtion mass spectrometry analysis showed that the expected peptide Leu psi[CH2N(CH2CH2CH2SH)]Ser-Pro-Gly-Lys-Val psi[CH2N(CH2CH2CH2-SH)] Ala-Pro-Lys-Tyr-NH2 was obtained as the major product with low levels of side products. Intramolecular oxidation of the thiols gave the backbone to backbone cyclized peptide Leu psi[CH2N(CH2CH2CH2S)]Ser-Pro-Gly-Lys- Val psi[CH2N(CH2CH2CH2-S)]Ala-Pro-Lys-Tyr-NH2.

Alkylation↗

PubMed1993

New method for the synthesis of N-methyl amino acids containing peptides by reductive methylation of amino groups on the solid phase.

Primary amino groups on the model peptide Xaa-Ala-Pro-Lys(ClZ)-Tyr(2BrZ), synthesized on a p-methylbenzhydryl amine resin with conventional Boc/benzyl protective group strategy, were reacted with 4,4'-dimethoxydityl chloride in dichloromethane, resulting in the introduction of the dimethoxydityl group, which is an acid-labile N-alkyl type of protective group. The secondary amino groups thereby formed can be methylated by treating the peptide-resin with formaldehyde and sodium cyanoborohydride in N,N-dimethylformamide. After the removal of the dimethoxydityl group with trifluoroacetic acid, the resulting N-methylated amino acid residues with a free secondary amino groups are accessible for acylation with the next activated Boc amino acid. With this method majority of the 20 common amino acids can be monomethylated directly on the resin and, in most cases, with very low levels of the side reactions. In the cases where the complete methylation is difficult to achieve, the remaining primary amino groups can be selectively acylated in the presence of secondary amino groups with trimethylacetic acid 1-hydroxybenzotriazole ester. The method provides a convenient general route to synthesize N-methylated derivatives of most of the occurring and synthetic amino acids.

Amino Acid Sequence↗