Copper(II) and zinc(II) ion binding properties of a MAP type branched ligand with histidines as surface functionalities.

A novel branched peptide type ligand consisting of three lysines as branching units and four histidines as functional groups has been designed and prepared by solid phase peptide synthesis. The N-terminal histidines offer eight primary protonation/metal ion binding sites: four amino and four imidazole groups, capable of binding up to two metal ions. We examined the protonation equilibria, and the complex formation processes with copper(II) and zinc(II) ions in c(M):c(L) = 1:1 and 2:1 initial concentration ratio in aqueous solutions.

Design of histidine containing peptides for better understanding of their coordination mode toward copper(II) by CD spectroscopy.

The systematic investigation of the copper(II) complexes of tripeptides Xaa-Xaa-His, Xaa-His-Xaa and His-Xaa-Xaa, where Xaa=Gly or Ala was performed by combined pH-metry, spectrophotometry, CD and in part EPR spectroscopy. The matrix rank analysis of the spectral data revealed the number of the coloured and optically active species as a basis for the solution speciation. A critical evaluation on the speciation and solution structure of the complexes formed is presented on the basis of their d-d band optical activity.

CD spectroscopic study on the speciation and solution structure of copper(II) complexes of some tripeptides in combination with potentiometric and spectrophotometric results.

The combination of potentiometric, spectrophotometric and CD spectroscopic studies under the same conditions is expected to yield more reliable thermodynamic and structural information for a certain system. The matrix rank analysis of both the spectrophotometric and CD spectra series gives the necessary number of species to be taken into account in the calculations. Based on such speciation diagrams the molar spectra for individual complexes in the copper(II) Gly-Gly-Ala, Gly-Ala-Gly, Ala-Gly-Gly and Ala-Ala-Ala systems were obtained.

[Synthesis of a cyclic enkephalin analog with prolonged action].

A cyclic analog of enkephalin, cyclo(Lys-Tyr-DMet-Gly-Phe-Pro-) and two corresponding linear hexapeptides with lysine residue on the N- and C-termini of the pentapeptide sequence, Lys-Tyr-DMet-Gly-Phe-Pro and Tyr-DMet-Gly-Phe-Pro-Lys were synthesized by classical and solid phase methods of peptide chemistry. The cyclic analog exhibited significantly prolonged analgesic effect, evaluated by the "tail pinch" method after intracysternal injection to mice. The cycloanalog also had a weak influence on the peripheral opiate receptors of the isolated segment of guinea pig iliac intestine.

[Synthesis and analysis of cyclic analogs of angiotensin].

Five angiotensin cycloanalogues have been synthesised by classical methods of peptide chemistry, cyclisation being carried out via pentafluorophenyl esters. Cycloanalogues (I-IV) with a fixed potential turn in the C-terminal part of the angiotensin molecule inferred on the basis of physico-chemical data do not possess angiotensin-like activity. Compounds (V) with enlarged cycle shows decreased pressor effects as compared with angiotensin.

[Synthesis and study of cyclic and linear analogs of neurotensin].

New cyclic analogues of neurotensin (NT): [cyclo (13----8), Gly8]NT-(8-13), [cyclo (13----7), Gly7]NT-(7-13), [cyclo (13----5 epsilon), Lys5]NT-(5-13), [cyclo (13----4 epsilon), Lys4]NT-(4-13), and their linear precursors have been synthesized. The latter (protected linear compounds) were prepared by solid-phase peptide synthesis, and cyclization was attained by using diphenylphosphoryl azide. Cyclization of C-terminal hexa- and octapeptide fragments of NT was found to lead to cycloanalogues possessing high depressor activity.

[Conformation of the enkephalin cycloanalog Lys-Tyr-Gly-Gly-Phe-Leu-].

The spatial structure of an enkephaline cycloanalogue Lys-Tyr-Gly-Gly-Phe-Leu--has been investigated by means of energy calculations, fluorescence and CD-spectroscopy. Despite the high conformational mobility of the cycloanalogue, little resemblance exists between its and parent peptide's low-energy structures. Conformational factors for possible mechanisms of interaction between specific enkephalin receptors and cycloanalogue are discussed.

[Synthesis and biological activity of cyclic and linear analogs of C-terminal fragments of neurotensin].

Using solid-phase approach, new cyclic and linear analogues of C-terminal neurotensin (NT) fragments were synthesized and their vasodepressor and miotropic activities were assayed. The cyclic structures were fixed by a peptide bond linking the lysine epsilon-amino group with the C-terminal carboxyl. Cyclization was performed by using pentafluorophenyl esters or diphenylphosphorylazide.

[Structural and functional organization of ACTH: synthesis and properties of analogs of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexa-amino acids instead of a natural sequence of ACTH 19-24 amino acids].

To assess the role of amino acid sequence ACTH 19-24 in the corticotropin structure and steroidogenic activity, the analogues of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexaglycine, hexaphenylalanine, hexaglutamic acid or hexalysine instead of the natural 19-24 sequence have been synthesized by conventional methods. All these compounds in water have the CD curves characteristic of random coil, CD spectra of analogue ACTH-(1-24)-tetracosapeptide and hexalysine-containing analogue ACTH-(11-24)-tetradecapeptide in trifluoroethanol indicate the presence of alpha-helices. The latter compound manifested higher steroidogenic activity than ACTH-(11-24)-tetradecapeptide.