The crystal structure of <i>S</i>-benzyl-<scp>L</scp>-cysteinyl-<scp>L</scp>-prolyl-<scp>L</scp>-leucylglycinamide and its selenium analog

Rudko, Andrew D.; Low, Barbara W.

doi:10.1107/s0567740875003676

Cited by 28 publications

(11 citation statements)

References 22 publications

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“…In contrast, strategies for construction of 13-hairpins have been less widely explored (27-32). Furthermore, crystallographic examinations have been made only in two-to five-residue acyclic peptides (33)(34)(35)(36)(37)(38)(39)(40). In this report we describe the crystal structure of a designed, synthetic 13-hairpin in an acyclic octapeptide.…”

Section: Introductionmentioning

confidence: 99%

A designed beta-hairpin peptide in crystals.

Karle

Awasthi

Balaram

1996

Proc. Natl. Acad. Sci. U.S.A.

168

123

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ABSTRACT13-hairpin structures have been crystallographically characterized only in very short acyclic peptides, in contrast to helices. The structure of the designed ,3-hairpin, t-butoxycarbonyl-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe in crystals is described. The two independent molecules of the octapeptide fold into almost ideal 13-hairpin conformations with the central D-Pro-Gly segment adopting a Type 1' 13-turn conformation. The definitive characterization of a 13-hairpin has implications for de novo peptide and protein design, particularly for the development of three-and four-stranded 13-sheets.De novo peptide and protein design is based on the ability to construct peptide sequences with predictable folding patterns (1-7). Helices and 13-sheets have been the focus of considerable synthetic attention in attempts to assemble mimics for helical bundles (8-11) and all 83-motifs (12-15). Helix nucleation strategies have been successful in generating both watersoluble helices, using stabilizing side chain interactions (16)(17)(18)(19), and incorporating backbone conformational constraints in hydrophobic helices (20)(21)(22). The ready crystallizability of peptide helices nucleated with a,a-dialkylated amino acids has permitted detailed stereochemical characterization by x-ray diffraction (23-26). In contrast, strategies for construction of 13-hairpins have been less widely explored (27-32). Furthermore, crystallographic examinations have been made only in two-to five-residue acyclic peptides (33)(34)(35)(36)(37)(38)(39)(40). In this report we describe the crystal structure of a designed, synthetic 13-hairpin in an acyclic octapeptide.Analysis of 13-hairpin structures in proteins reveal that such features invariably contain Type II' or I' 13-turns as the nucleating segment of the chain reversal (41-43). We therefore designed the octapeptide t-butoxycarbonyl (Boc)-LeuVal-Val-D-Pro-Gly-Leu-Val-Val-OMe (11) such that the central D-Pro-Gly segment facilitates a Type II' 13-turn conformation. The constraint of pyrrolidine ring formation in D-Pro restricts the value of 4 to +60°+ 20°. The idealized conformational angles for the i+ 1/i+2 residues of a Type II' 13-turn are: 0j+1 = +600, qAj+, = -120°, 4i+2 = -80°, and q/i+2 = 0°( 44, 45). The valine-rich arms are expected to favor extended strand conformations in view of the established propensity of 13-branched residues to occur in 13-sheets in proteins (46-48). EXPERIMENTAL METHODSThe peptide was synthesized by conventional solution phase procedures and purified by medium pressure liquid chromatography on a C18 column (40-60 microns), followed by HPLC purification on a C18 column (10 microns) using methanolwater gradients. The peptide was fully characterized by 400 MHz 'H NMR (49).Colorless crystals in the form of very thin plates were grown by slow evaporation from a CH30H solution, to which a small amount of water was added. Almost all the crystals were composites in the form of a stack of several thin wafers. The crystal selected for data collection had a slightly sp...

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Section: Introductionmentioning

confidence: 99%

A designed beta-hairpin peptide in crystals.

Karle

Awasthi

Balaram

1996

Proc. Natl. Acad. Sci. U.S.A.

168

123

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“…A similar situation occurs in eyclo (-L-histidyl-L-aspartyl-)trihydrate (Ramani, Venkatesan & Marsh, 1978). As noted by Lin & Webb (1973) References: (1) present paper; (2) Benedetti, Palumbo, Bonora & Toniolo (1976); (3) Cotrait, Geoffre, Hospital & Preeigoux (1979); (4) Rudko & Low (1975).…”

Section: C~(i)-c?(i)-ct~(i)--c/oel(i)mentioning

confidence: 74%

Structure of the tetrapeptide L-methionyl-L-α-glutamyl-L-histidyl-L-phenylalanine monohydrate, C25H34N6O7S.H2O

Admiraal¹,

Vos²

1983

Acta Crystallogr C

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“…Rappelons d'ailleurs que des fl turns ont 6tb observes fi l'&at solide pour un nombre important d'oligopeptides poss6dant un reste Pro: c'est le cas notamment pour un certain nombre de substrats de la collag6nase comme N-benzyloxycarbonyl-Gly-Pro-Leu-Gly-Pro-OH (Bando, Tanaka, Ashida & Kakudo, 1978), le t&rapeptide terminal de l'oxytocine Cys-Pro-Leu-Gly-NH 2 (Rudko & Low, 1975).…”

Section: Discussionunclassified

Etude conformationnelle par diffraction des rayons X et calcul théorique du fragment 23-26 de l'ACTH; Ac-Tyr-Pro-Asn-Gly-OH, C₂₂H₂₉N₅O₈.0,7C₂H₆OS

Cotrait¹,

Geoffre²,

Hospital³

et al. 1983

Acta Crystallogr Sect B

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INFLUENCE OF HYDROGEN BONDS ON MOLECULAR CONFORMATIONenergy. This result is more in agreement with the previously mentioned NMR data than the results from the calculations with e = 1. Future calculations on saccharides will decide whether e = 3 should be used in the case of intramolecular energies, or that the apparent disagreement between experimental and theoretical results is due to the packing effects described above. (1979). Acta Cryst. B35, 656-659. ELIEL, E. L., ALLINGER, N. L., ANGYAL, S. J. & MORRISON, G. A. (1965). In Conformational Analysis, Ch. 6. New York: Wiley Interscience. HOUGH, E., NE1DLE, S., ROGERS, D. & TROUGHTON, P. G. H. (1973). Acta Crvst. B29, 365-367. JEFFREY, G. A. (1982 AbstractA conformational study of Ac-Tyr-Pro-Asn-Gly-OH, the 23-26 ACTH fragment, is presented, in the solid state using X-ray analysis (Cu K~t) and in the isolated state by empirical calculations. Monoclinic, P2~, a --9.574 (3), b = 9.831 (3), c = 15-707 (4)A, fl 103.06 (1) °, V = 1440 A 3, Z = 2. In the crystal, the tetrapeptide has an approximately stretched conformation and is involved in numerous intermolecular hydrogen bonds; this conformation is rather close to those of its zwitterionic form. Theoretical calculations show that the most stable conformation (by 11-25 kJ mol -~) is the (Pro2-Tyr 3) fl turn III. It is followed by numerous partially or fully stretched structures as well as the (Pro2-Tyra) fl turns II and I. It appears that such a short peptide may adopt various conformations in a limited range of energy, some of which may be stabilized by surrounding molecules.L'hormone adr6nocorticotrope (ACTH) est un peptide lin6aire, constitu6 de 39 acides amines, produit par l'hypophyse ant6rieure. Son action biologique prin-0108-7681/83/060754-07501.50 cipale est la stimulation et la r~gulation de la s6cr6tion des corticost6ro'ides (Sayers, Beall & Seelig, 1974). De nombreuses &udes ont montr6 que I'ACTH et certains de ses fragments sont aussi impliqubs dans le processus comportemental chez l'animal (de Wied, 1974). Les ~tudes physicochimiques les plus r~centes: par dichro'isme circulaire, RMN et predictions conformationnelles (Toma, Greff, Fermandjian, L6w & Kisfaludy, 1976; Toma, Fermandjian, L6w & Kisfaludy, 1978;Mutter, Mutter & Bayer, 1979) sont plus ou moins en faveur d'une structure non ordonn+e pour I'ACTH 16-22 ou 17-24 mais sont en d6saccord en ce qui concerne la partie C-terminale. Par exemple, Jibson & Li (1979) concluent fi la formation d'un 'fl turn' pour le fragment 23-26 suivi d'une h61ice a pour la s6quence 27-35 tandis que Mutter et al. (1979) inclinent pour une structure non ordonn~e suivie par une structure en feuillet tip.Pour apporter un 6clairage nouveau fi ce probl6me, nous avons synth6tis6, cristallis6, &abli la structure cristalline du fragment 23-26 et calcul6 les conformations les plus probables du t~trapeptide. Partie exp~rlmentale Synth~.ses et purificationsOH ont 6t6 synth&is6s en phase solide. La synth6se a 6t6 effectu6e sur un appareil automatique mis au point au labor...

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The crystal structure of S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide and its selenium analog

Cited by 28 publications

References 22 publications

A designed beta-hairpin peptide in crystals.

A designed beta-hairpin peptide in crystals.

Structure of the tetrapeptide L-methionyl-L-α-glutamyl-L-histidyl-L-phenylalanine monohydrate, C25H34N6O7S.H2O

Etude conformationnelle par diffraction des rayons X et calcul théorique du fragment 23-26 de l'ACTH; Ac-Tyr-Pro-Asn-Gly-OH, C₂₂H₂₉N₅O₈.0,7C₂H₆OS

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The crystal structure of S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide and its selenium analog

Cited by 28 publications

References 22 publications

A designed beta-hairpin peptide in crystals.

A designed beta-hairpin peptide in crystals.

Structure of the tetrapeptide L-methionyl-L-α-glutamyl-L-histidyl-L-phenylalanine monohydrate, C25H34N6O7S.H2O

Etude conformationnelle par diffraction des rayons X et calcul théorique du fragment 23-26 de l'ACTH; Ac-Tyr-Pro-Asn-Gly-OH, C22H29N5O8.0,7C2H6OS

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Etude conformationnelle par diffraction des rayons X et calcul théorique du fragment 23-26 de l'ACTH; Ac-Tyr-Pro-Asn-Gly-OH, C₂₂H₂₉N₅O₈.0,7C₂H₆OS