- The molecular basis for the selection of captopril cis and trans conformations by angiotensin I converting enzyme
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Enzyme-inhibitor recognition is considered one of the most fundamental aspects in the area of drug discovery. However, the molecular mechanism of this recognition process (induced fit or prebinding and adaptive selection among multiple conformers) in several cases remains unexplored. In order to shed light toward this step of the recognition process in the case of human angiotensin I converting enzyme (hACE) and its inhibitor captopril, we have established a novel combinatorial approach exploiting solution NMR, flexible docking calculations, mutagenesis, and enzymatic studies. We provide evidence that an equimolar ratio of the cis and trans states of captopril exists in solution and that the enzyme selects only the trans state of the inhibitor that presents architectural and stereoelectronic complementarity with its substrate binding groove.
- Tzakos, Andreas G.,Naqvi, Nawazish,Comporozos, Konstantinos,Pierattelli, Roberta,Theodorou, Vassiliki,Husain, Ahsan,Gerothanassis, Ioannis P.
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- The solid phase synthesis of peptides containing an arginine residue with an unprotected guanidine group
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A new variant of the solid phase synthesis of arginine-containing peptides was proposed. The conditions for the attachment to the Wang polymer of Nα-Fmoc-arginine containing a protonated guanidine group were found. We demonstrated that this attachment is accompanied by neither racemization nor the attachment of the second Arg residue. Side reactions involving the guanidine group of arginine were studied, and methods for their prevention were proposed. The comparison of the carbodiimide method with a 1-hydroxybenzotriazole additive and a modified method with the use of Kastro's reagent for the introduction of Nα-Fmoc-Arg residue with the unprotected guanidine group into the growing peptide chain demonstrated the advantages of the second method. Bradykinin and a peptide corresponding to the 584-591 sequence of the transmembrane gp41 from HIV-1 were synthesized by the method proposed here.
- Rubina,Bespalova,Bushuev
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- γ-Valerolactone (GVL): An eco-friendly anchoring solvent for solid-phase peptide synthesis
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Due to the hazardous nature of CH2Cl2, regulatory authorities have imposed restrictions to minimize or even stop its use. It has therefore become imperative to identify environmentally benign solvents to replace it. Here we report on a bio derived solvent, γ-valerolactone, for the incorporation of the first amino acid onto p-alkoxybenzyl alcohol resin in solid-phase peptide synthesis. Satisfactory loading values (by a spectrophotometric method) were achieved. Furthermore, racemization and dipeptide formation were also checked and found to be acceptable.
- Al Musaimi, Othman,El-Faham, Ayman,Basso, Alessandra,de la Torre, Beatriz G.,Albericio, Fernando
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- PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
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Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.
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- Trends in asymmetric Michael reactions catalysed by tripeptides in combination with an achiral additive in different solvents
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The potential of tripeptides 3, 6 and 12 as chiral catalysts for asymmetric Michael addition reactions in the presence of an achiral additive has been tested in different solvents (CHCI3, acetone, DMF, DMSO and the room-temperature ionic liquid
- Tsogoeva, Svetlana B.,Jagtap, Sunil B.,Ardemasova, Zoya A.,Kalikhevich, Victor N.
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p. 4014 - 4019
(2007/10/03)
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- Synthesis of Ethylamide of Cyclic Undecapeptide Corresponding to the 593 - 603 Sequence of Transmembrane Glycoprotein gp41 of Human Immunodeficiency Virus Type Two
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Ethylamide of cyclic disulfide of the HIV-2 peptide antigen corresponding to the 593 - 603 sequence of the gp41 protein was synthesized by conventional methods of peptide chemistry in solution.The absence of racemization during fragment condensation was s
- Sidorova, M. V.,Kudryavtseva, E. V.,Molokoedov, A. S.,Ovchinnikov, M. V.,Bespalova, Zh. D.
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p. 582 - 589
(2007/10/03)
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- Cardiac atrial peptides
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A DNA fragment encoding at least part of the ANF protein has been molecularly cloned and its nucleotide sequence partially determined. The composition and sequence of a peptide containing 116 amino acids within the ANF gene have been determined. Biologically active subunit peptides have been identified.
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- ATRIOPEPTINS. I. SYNTHESIS OF C-TERMINAL FRAGMENTS
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Peptides, corresponding to the C-terminal sequence in atriopeptins, have been synthesized using classical methods of peptide synthesis in solution and characterized by various physicochemical methods.The synthetic strategy and methods are discussed.
- Ovchinnikov, Mikhail V.,Bespalova, Zhanna D.,Molokoedov, Aleksandr S.,Revenko, Inna V.,Sepetov, Nikolai F.,et al
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p. 772 - 783
(2007/10/02)
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- SYNTHESIS OF DINITROPHENYLTETRAPEPTIDES AS CHROMOPHORIC SUBSTRATES OF ENDOPROTEINASES
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The synthesis has been performed of ten tetrapeptides of the general formula Dnp-Gly-Gly-X-Arg-OH, where X = Val, Phe, Abu, Asp(OBut), Asp, Met, D-Phe, Ser, Thr, or Trp.The synthesis was carried out with Dnp-Gly-Gly-Onp, activated esters of pro
- Kulikov, S. V.,Sokolova, N. Yu.,Rodin, S. V.,Samartsev, M. A.
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p. 469 - 475
(2007/10/02)
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