Characterization of Four Amino Acids Constituting Cyl-2, a Metabolite from<i>Cylindrocladium scoparium</i>

Hirota, Akira; Suzuki, Akira; Tamura, Saburo

doi:10.1080/00021369.1973.10860788

Cited by 13 publications

(2 citation statements)

References 3 publications

(4 reference statements)

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“…The phenylalanine stereochemistry of WF-3161, although originally reported as L-Phe, was later revised to D-Phe on the basis of spectroscopic and chemical studies [70]. The fungus Cylindrocladium scoparium produced the prolyl-substituted Cyl-1 (40) as well as its pipecolyl-variant Cyl-2 (41); both were potent plant growth regulators [71][72][73]. The absolute stereochemistry of the Aoe moiety in Cyl-2 was determined using CD spectroscopy [74].…”

Section: Cyclic Histone Deacetylase In-hibitorsmentioning

confidence: 99%

Histone Deacetylase: A Target for Antiproliferative and Antiprotozoal Agents

Meinke¹,

Liberator²

2001

CMC

108

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Histone deacetylase (HDAC) and histone acetyltransferase (HAT) are enzymes that influence transcription by selectively deacetylating or acetylating the eta-amino groups of lysines located near the amino termini of core histone proteins. It is well-established that in transcriptionally active chromatin, histones generally are hyperacetylated and, conversely, hypoacetylated histones are coincident with silenced chromatin. Revived interest in these enzymatic pathways and how they modulate eukaryotic transcription has led to the identification of multiple cofactors whose complex interplay with HDAC affects gene expression. Concurrent with these discoveries, screening of natural product sources yielded new small molecules that were subsequently identified as potent inhibitors of HDAC. While predominantly identified using antiproliferative assays, the biological activity of these new HDAC inhibitors also encompasses significant antiprotozoal, antifungal, phytotoxic and antiviral applications. These newly discovered HDAC inhibitors served as lead structures for the development of improved derivatives including related reagents with considerable potential as tools to further elucidate the mechanism of transcriptional regulation.

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Section: Cyclic Histone Deacetylase In-hibitorsmentioning

confidence: 99%

Histone Deacetylase: A Target for Antiproliferative and Antiprotozoal Agents

Meinke¹,

Liberator²

2001

CMC

108

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“…Tentoxin (1) 1,2 and AM-toxin I (2), 3,4 characterized by three L-amino acids and one ␣,␤-dehydrogenated residue (Figure 1), exhibit host or non host-specific phytotoxic activities. Cyl-1 (3), 5 Cyl-2 (4), 6,7 and HC-toxin (5), 8 -11 which are also phytotoxic peptides, possess a D-residue instead of the dehydro-residue, and are marked by the presence of a novel amino acid residue, L-Aoe. The presence of L-Aoe and the analogous residue L-Aod also characterizes the next group of cyclotetrapeptides in Table I comprising chlamydocin (6), [12][13][14] trapoxin A (7), trapoxin B (identical to trapoxin A with a D-Pro residue in place of the D-Pip residue), 15 apicidin (8), apicidin A [identical to Apicidin with L-Trp in place of L-Trp(N-OMe)], 16 and WF-3161 (9).…”

Section: Introductionmentioning

confidence: 99%

Predicting the conformational states of cyclic tetrapeptides

et al. 2003

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Biologically active cyclic tetrapeptides, usually found among fungi metabolites, exhibit phytotoxic or cytostatic activities that are likely to be governed by specific conformations adopted in solution. For conformational studies and drug design, there is a strong interest in using fast and reliable methods to determine correctly the conformational population of cyclotetrapeptides. We show here that standard molecular mechanics computational approach gives satisfactory results. The method was validated step by step by experimental data either obtained after synthesis and NMR analysis, or found in the literature. The cyclo(Gly)(4), cyclo(Ala)(4), cyclo(Sar)(4), and cyclo(SarGly)(2) peptides were used to evaluate the prediction of the peptide backbone conformation, and the detailed conformational analysis of tentoxin, a natural phytotoxic cyclotetrapeptide in which N-alkylated peptide bonds alternate with regular secondary ones, was used to validate the computation of conformers proportions. From the knowledge of an initial cyclic primary structure and of the D or L configuration of the amino acids, we show that it is possible to determine the exact orientation of carbonyl groups and to predict the nature of conformers present in solution. The proportion of each conformer can be inferred from a statistical thermodynamics approach by using the potential energy values of each conformer, computed by molecular mechanics methods with the TRIPOS force field, which allowed us to account for the solvent. The solvent contribution was processed by two different methods according to the nature of the interactions: whether through the dielectric constant introduced in the electrostatic potential, when interaction with solute molecules are weak or negligible, or through the computation of free energy of solvation using the algorithm SILVERWARE for solvents explicitly interacting with the solute. When applied to tentoxin, this conformational analysis yielded results in very good agreement with the experimental data reported by Pinet et al. (Biopolymers, 1995, Vol. 36, pp. 135-152), on both the nature of existing conformers and their relative proportions, whatever the nature of the considered solvent.

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