Molecular and crystal structures of two β-bend forming monothiated analogues of melanostatin

Bardi, R.; Piazzesi, A. M.; Toniolo, Claudio; Jensen, O. E.; Andersen, T. P.; Senning, Alexander

doi:10.1016/s0040-4020(01)86115-9

Cited by 25 publications

(12 citation statements)

References 25 publications

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“…The results of these studies show that the structure of the thiopeptide unit (thioamide) is indeed very similar to that of the peptide bond. However, differences in electronic properties between the 0-and S-atom sometimes, cause several interesting structural consequences in peptides containing this 'isosteric replacement' [22].…”

Section: B R = M E S C R = Ets D R = S V C H 2 a -Tmentioning

confidence: 99%

“…Parameters for the C=S bond are not included in the standard GROMOS package, therefore, we used the reported value of 1.66 8, (for thiopeptides) for the C=S bond length [19c] [22] [32], although slightly shorter and longer distances were published. Further bond lengths and angles were not changed; they are very similar to those which are known from amides [72].…”

Section: Assignment Of H-c(a) and R -C ( A ) Instead Of H-c@) And H'-mentioning

confidence: 99%

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Thiocyclosporins: Preparation, Solution and Crystal Structure, and Immunosuppressive Activity

Seebàch¹,

Kessler

et al. 1991

Helvetica Chimica Acta

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The reaction of cyclosporin A (CsA) with Lawesson's reagent under different conditions yields various thiocyclosporins, in which carbonyl 0-atoms and/or the hydroxy 0-atom of the MeBmt residue are replaced by an S-atom. The position of the S-atom is determined by NMR spectroscopy, and the conformations of the products are studied by NMR spectroscopy and X-ray crystallography. Some of the thiocyclosporins show interesting conformational properties. Whereas one conformation strongly dominates for CsA in CDCl,, two conformers A and B, in a ratio 58:42 are found for ['yl',CS-NH]CsA, Extensive NMR studies including new 2D and 3D heteronuclear techniques and restrained MD calculations using ROE effects demonstrate that the major conformer

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Section: B R = M E S C R = Ets D R = S V C H 2 a -Tmentioning

confidence: 99%

Section: Assignment Of H-c(a) and R -C ( A ) Instead Of H-c@) And H'-mentioning

confidence: 99%

Thiocyclosporins: Preparation, Solution and Crystal Structure, and Immunosuppressive Activity

Seebàch¹,

Kessler

et al. 1991

Helvetica Chimica Acta

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“…Thioxo amides are stronger acids [lo] but weaker bases than amides [ll]. Nevertheless, the introduction of a thioxo amide bond is a nearly isosteric substitution for an amide bond [12] often accompanied with surprising effects on the conforma-tion of peptides [13,141 and on the proteolytic stability [ 15 -…”

mentioning

confidence: 99%

Influence on proline‐specific enzymes of a substrate containing the thioxoaminoacyl–prolyl peptide bond

Schutkowski

Neubert

Fischer³

1994

European Journal of Biochemistry

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Dipeptidyl peptidase IV from porcine kidney and aminopeptidase P from Escherichia coli can utilize thioxoalanyl-proline 4-nitroanilide but with decreased kinetic constants compared to the normal substrates. Product analysis showed that exclusively thioxoalanyl-proline was liberated in the case of dipeptidyl peptidase IV catalysis and thioxo-alanine in the case of aminopeptidase-P-mediated thioxo peptide bond hydrolysis. For the proline-specific aminopeptidase P the k,,/K,,, value for the thioxo peptide is 1100-fold lower than for the corresponding 0x0 peptide. This difference is entirely due to k,,,. Because the rotation about the thioxo amide bond is about 12.5 kJ mol-' more difficult than rotation about an amide bond, these data support a mechanism involving rate-limiting rotation about the scissile peptide bond. It was found that the specificity rate constant for the reaction of thioxoalanyl-proline 4-nitroanilide and dipeptidyl peptidase IV is 100 -1000-fold lower compared to the corresponding rate constant for alanyl-proline 4-nitroanilide. This remarkable effect is interpreted in terms of a distorted binding of the transition state for the thioxo substrate. The hydrolysis of the thioxo substrate by dipeptidyl peptidase IV is isomer-specific. The conformation about the nonscissile P,-PI thioxo amide bond has to be in trans for successful cleavage of the scissile peptide bond. We can now directly compare the rotational energy barrier of the prolyl peptide bond for the 0x0 and the thioxo form.Modification of the backbone of biologically active peptides has become increasingly important in the design of analogues possessing greater potency and enzymatic stability. Peptide bond modifications often induce drastic changes in flexibility of the peptide backbone. In contrast X-ray [l], infrared [2], CD [3] and NMR [4J studies of simple thioxo di-and tri-peptides have revealed that a thioxo amide mainly adopts a Z planar configuration similar to an amide, except that the thioxo-carbonyl bond is longer (C=O = 0.124 nm, C=S = 0.164 nm) [l, 51. Furthermore, the larger covalent [6] and van der Waals [7] radius of sulfur restricts the allowable $,iy angles in the vicinity of thioxo amides [8]. Thioxo peptides are also known to display a higher barrier of rotation about the C-N bond by 8-12 kJ/mol [9]. Amides and thioxo amides differ also in their hydrogen-bond forming properties. Thioxo amides are stronger acids [lo] but weaker bases than amides [ll]. Nevertheless, the introduction of a thioxo amide bond is a nearly isosteric substitution for an amide bond [12] often accompanied with surprising effects on the conformaCorrespondence to M. Schutkowski, Max-Planck-Gesellschaft zu Forderung der Wissenschaft e. V.,

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“…In general, in thioxopeptides units there are only minor deviations from the planar trans form ( ω = 180°). An intramolecular C′S…HN H‐bond, although weak, was first observed for a type‐II β‐turn forming, fully protected, tripeptide amide . The N…S separation is 3.56 Å, less than the outer limit of 3.7 Å.…”

Section: Resultsmentioning

confidence: 95%

Endothioxopeptides: A conformational overview

et al. 2016

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Although thionamides would have been first prepared two centuries ago and their chemical and spectroscopic properties extensively investigated, only much more recently (since about 1985) a well deserved but still insufficient attention has been paid to their endothioxopeptide subfamily which nonetheless currently represents a rapidly emerging area of great scientific interest in the broader field of foldameric compounds based on biologically relevant building blocks. After two brief sections offering information on the unfortunately still limited number of endothioxopeptides discovered from natural sources but also on the impressive advancements registered in the last few years in their synthetic methods, this review article outlines the results of a detailed literature survey on the ongoing great, but not systematic, progress related to the conformational consequences generated by incorporating one (or more) thionamide group(s) into a polypeptide chain. Finally, a short discussion of the growing, but still in its infancy, class of the endoselenoxopeptide congeners is also presented.

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Molecular and crystal structures of two β-bend forming monothiated analogues of melanostatin

Cited by 25 publications

References 25 publications

Thiocyclosporins: Preparation, Solution and Crystal Structure, and Immunosuppressive Activity

Thiocyclosporins: Preparation, Solution and Crystal Structure, and Immunosuppressive Activity

Influence on proline‐specific enzymes of a substrate containing the thioxoaminoacyl–prolyl peptide bond

Endothioxopeptides: A conformational overview

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