Conformational studies of corticotropin1–32 and constitutive peptides by circular dichroism

Greff, Daniel; Toma, Flavio; Fermandjian, Serge; Low, Martin G.; Kisfaludy, L.

doi:10.1016/0005-2795(76)90177-x

Cited by 51 publications

(26 citation statements)

References 16 publications

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“…Whereas the pH dependence of the difference spectra is well correlated between the ' L b and 'Lo, ' B bands in these peptides, it is surprising that the rather remarkable solvent effect of FsEtOH in the near-ultraviolet CD spectra is so weakly evident in the peptide region, especially with respect to residue 8. In this context we are reminded of the fact that the solvent effect H,0/F3EtOH for the entire far-ultraviolet CD spectrum of bradykinin, as shown by Marlborough et al [9] and confirmed by our studies, is rather small in comparison to what has been observed in the case of angiotensin 11 [26] and adrenocorticotropin [27]. Evidently the three transitions 'Lb, ' L , and ' B are not affected equally every time an outer parameter changes in any way.…”

Section: Spectra In the Far-ultraviolet Regionsupporting

confidence: 79%

Conformational Features of Bradykinin

Lintner¹,

Fermandjian²,

Regoli³

et al. 1977

European Journal of Biochemistry

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The circular dichroism (CD) of the peptide hormone bradykinin and its analogues, [Phe(€L)']-bradykinin, [Phe(H4)*]bradykinin, [Phe(H4)5.8]bradykinin, [TyrOMe'Ibradykinin, [TyrOMe'Ibradykinin and [TyrOMeS3']bradykinin, is described. The comparison of the CD spectra of these analogues with each other, recorded under a variety of conditions (pH, solvent, temperature), allows the monitoring of the behaviour of the aromatic side-chains (phenylalanine, tyrosine) and an estimation of their respective spectral contributions in both spectral regions (320-250 nm, 250-190 nm) with good precision. Conformational non-equivalence of the residues Phe-5 and Phe-8 together with some overall conformational features of bradykinin are thus established.The peptide hormone bradykinin has so far presented stimulating challenges to those who have tried to elucidate its primary sequence [I], its physiological role and significance [2], its pharmacology 131 and its conformation in solution [4-121. In spite of its rather simple amino acid sequence : Arg-Pro-Pro-Gly-PheSer-Pro-Phe-Arg, it has neither been possible to establish a coherent structure-activity relationship (the term structure involving both composition and conformation), as no antagonist of importance has yet been synthesized, nor has a clearcut picture of its solution conformation emerged from the relatively few and sometimes conflicting and/or contradicting studies [5,6,10]. Nevertheless, specific receptors in rabbit aorta and guinea-pig ileum have now been found, and all the recent experimental evidence hints strongly at the existence of a restricted number of close conformational states of bradykinin, be it in aqueous or organic solvent, as a look at its amino acid composition and sequence already suggests [13]. Our contribution to the conformational analysis of this hormone will begin with a detailed examiiiation by circular dichroism spectroscopy of the aromatic side-chains (Phe-5, Phe-S), their spectral contribution and their conformational behaviour, which should help to shed further light on the structural characteristics of bradykinin.Of all the papers related to bradykinin conformation published up till now, only one (Brady et czl. [ S])Abbrrvintions. CD, circular dichroism; NMR, nuclear magnetic resonance: Phe( H 4 , cyclohexylalanine; TyrOMe, 0-methylated tyrosine; P3EtOH, 2.2,2-trifluoromethanol. MATERIALS AND METHODSBradykinin and its analogues used in the present experiments were prepared by the Merrifield method of solid-phase synthesis [33]. Details for the procedures and methods used in the synthesis, the purification and the chemical analysis of the newly synthesized peptides have been recently described [34].CD Studies. The peptides were dissolved in water or 2,2,2-trifluoroethanol (F3EtOH) (Uvasol, Merck) in concentrations ranging from 0.3 -1 .O mgiml wherc no aggregation takes place [7]. For the pH studies we

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Section: Spectra In the Far-ultraviolet Regionsupporting

confidence: 79%

Conformational Features of Bradykinin

Lintner¹,

Fermandjian²,

Regoli³

et al. 1977

European Journal of Biochemistry

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“…Behavioural studies with ACTH 4-9 and ACTH 4-10, in which the amino acid residues at sites 4 and 7 or 8 were modified, have given rise to the hypothesis that the molecules have a loop or helix-like structure in which Met ~ comes close to Arg ~ and Phe 7 (Greven & de Wied, 1980). This hypothesis has been supported by circular-dichroism studies (Greff, Toma, Fermandjian, L6w & Kisfaludy, 1976). In crystals of ACTH 4-10 the molecules have the extended conformation and form an antiparallel fl sheet (Admiraal, 1981;Admiraal & Vos, 1983).…”

supporting

confidence: 51%

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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“…The importance of an amphiphilic a-helix in the region [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] ofcalcitonin has been demonstrated in previous analogues we have described. The most potent of these previous analogues is MCt-II, which has no hydrophilic residues interrupting the hydrophobic face of the amphiphilic a-helix.…”

Section: Discussionmentioning

confidence: 99%

“…Circular dichroism spectra of MCt-III were taken on an Aviv (Philadelphia) modification of a Cary model 60ds spectropolarimeter. All spectra were recorded in filtered 0.16 M KCI/0.02 M phosphate buffer, pH 7.4, or alternatively this same buffer system plus 50% trifluoroethanol (a structure-inducing solvent) (12). High-concentration scans were done in a 0.5-mm cell, whereas the lowerconlcentration scans were done in a 2-cm cell.…”

mentioning

confidence: 99%