Structure-activity relationships in the dodecapeptide .alpha. factor of Saccharomyces cerevisiae

Shenbagamurthi, P.; Baffi, R.A.; Khan, Sundas; Lipke, Peter N.; Pousman, C; Becker, Jeffrey M.; Naider, Fred

doi:10.1021/bi00274a047

Cited by 37 publications

(44 citation statements)

References 13 publications

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“…For simplicity, we use the abbreviated notations: the natural a-mating factor is denoted as (1 -13)peptide, and the des-Trp' dodecapeptide as (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)peptide. Thus, truncated peptides are denoted with the numbering of the N-terminal and C-terminal residues.…”

Section: Methodsmentioning

confidence: 99%

“…It may readily be noted that these peptides are classified into three groups, A,, A, and B, from the spectral patterns of amide proton resonances, especially in the region 8.5 -8.0 ppm. The group B includes the inactive analogs, (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13), (3)(4)(5)(6)(7)(8)(9)(10) and his^] (1 -13)peptide, and a number of N-H proton resonances of this group are localized around 8.4-8.3 ppm. The group A, includes active (1-n)peptides (n = 13, 12 and 10) and inactive (1 -9)peptide, and the group A, includes active (2-n)peptides ( n = 13 and 12) and inactive (2-9)peptide.…”

Section: Spectral Pattern Of Amide Proton Resonancesmentioning

confidence: 99%

“…For (3 -13), (3)(4)(5)(6)(7)(8)(9)(10) and [~His'](l-13)peptides, isolated resonances due to main-chain N-H protons of Gly9, Gln" and TyrI3 residues were assigned as shown in Fig. 2, while the N…”

Section: Assignments Of N-h Proton Resonances Of Group B Peptidesmentioning

confidence: 99%

“…Masui et al have reported that the activity of a-mating factor is not affected if the N-terminal Trp' residue is deleted [7], although Shenbagamurthi et al have recently reported that the dodecapeptide is less active than a-mating factor [lo]. However, if the two residues (Trp' and His') are eliminated, the truncated peptide, (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)peptide, shows no activity. On the other hand, the successive truncation of the C-terminal residues lowers the biological activity step by step.…”

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confidence: 99%

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Nuclear‐magnetic‐resonance studies on the conformations of tridecapeptide α‐mating factor from yeast Saccharomyces cerevisiae and analog peptides in aqueous solution

Higashijima

Masui

Chino

et al. 1984

European Journal of Biochemistry

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The conformation of tridecapeptide α‐mating factor from yeast Saccharomyces cerevisiae in aqueous solution was analyzed, in comparison with those of active analog and inactive analog peptides. 270‐MHz 1H‐NMR spectra of these peptides were observed and the spectral patterns of main‐chain N‐H proton resonances were classified into three groups, α‐mating factor and Trp1‐bearing active peptides belong to the group A1, active des‐Trp1‐peptides belong to the group A2 while the peptides of group B are inactive. The main‐chain N‐H proton resonances of the groups A1 and A2 and side‐chain N‐H proton resonances were all assigned to individual residues. The 13C‐NMR analysis of α‐mating factor indicates that the Lys7‐Pro8 and Gln10‐Pro11 peptide bonds exclusively take the trans form. From the temperature and pH dependences of chemical shifts and Gd(III)‐induced relaxation enhancements of amide proton resonances, α‐mating factor is found to take partly a folded conformation in aqueous solution, with an α‐helical form in the N‐terminal domain and two β‐turn forms in the central and C‐terminal domain. The pH dependence of fluorescence intensity indicates that, in this folded conformation, the C‐terminal carboxylate group lies close to the N‐terminal domain. The presence of the folded form in the N‐terminal domain and the β‐turn form in the central domain correlates with the biological activity of α‐mating factor and analog peptides. However, the folded conformation of α‐mating factor is in equilibrium with predominantly unordered form, as found from the circular dichroism and NMR analyses. The N‐H proton and C‐α proton resonances of free α‐mating factor as assigned in the present study allow the transferred nuclear Overhauser enhancement (NOE) analysis of the membrane‐bound conformation that is more directly related with the activity.

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Section: Methodsmentioning

confidence: 99%

Section: Spectral Pattern Of Amide Proton Resonancesmentioning

confidence: 99%

Section: Assignments Of N-h Proton Resonances Of Group B Peptidesmentioning

confidence: 99%

mentioning

confidence: 99%

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Nuclear‐magnetic‐resonance studies on the conformations of tridecapeptide α‐mating factor from yeast Saccharomyces cerevisiae and analog peptides in aqueous solution

Higashijima

Masui

Chino

et al. 1984

European Journal of Biochemistry

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“…A previous report found that dodecapeptide α-factor extended at the C-terminus with non-amino acids such as polyethylene glycol (PEG) is neither active in morphogenesis assay nor binding assay. 4,49 Therefore, the fairly high affinity of Cterminal extended analogs 1-6 ranging from 10% to 70% compared to that of native pheromone indicated that Trp extension has certain additional effects upon receptor binding. These effects include penetration of the ligand toward receptor site 1, which is the hydrophobic C-terminal binding pocket surrounded by transmembrane domain helix bundles.…”

Section: 1042mentioning

confidence: 99%

Highly Active Analogs of α-Factor and Their Activities Against Saccharomyces cerevisiae

Ahn¹,

Hong²,

Jin³

et al. 2014

Bulletin of the Korean Chemical Society

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Thirteen analogs of tridecapeptide α-factor (WHWLQLKPGQPMY) of Saccharomyces cerevisiae with C-or N-terminal Trp extension and isosteric replacement by Aib at position 8 and 11, Trp at position 13, D-Ala at position 9, and Orn and Glu at position 6 were synthesized and assayed for their biological activity. Receptor binding assay was carried out using our newly developed spectrophotometric method with detector peptide 14. C-or N-terminal extended analogs, α-factor-[Trp] n (n =1-5) 1-5 and [N-Trp] 1 -α-factor 6, were all less active than native α-factor and gradual decreases in both activity and receptor affinity were observed with greater Trp extension. Trp-substituted analog at position 13, [Trp 13 ]α-factor 7, exhibited about 2-fold reductions in both activity and receptor affinity. Aib-substituted analogs, [Aib 8 ]α-factor 8 and [Aib 11]α-factor 9, showed 5-to 10-fold reduction in activity as well as 3-fold reduction in receptor affinity compared to native α-factor. [Orn 6]α-factor 10 demonstrated strong potency with a 7.0-fold increase in halo activity as well as 1.8-fold increase in receptor affinity compared to native α-factor. ]α-factor 11 exhibited 15-fold higher halo activity as well as nearly 3-fold higher receptor affinity compared to native α-factor.

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A type II β‐turn in a flexible peptide: Proton assignment and conformational analysis of the α‐factor from saccharomyces cerevisiae in solution

et al. 1988

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SynopsisTwo-dimensional 'H-nmr spectra of the a-mating factor [in dimethyl sulfoxide-d, (DMSO) and in water] and several dodecapeptide analogues (in DMSO) were obtained. Homonuclear correlated spectroscopy resulted in the complete and unequivocal assignment of all backbone and side-chain resonances of the peptides. The solution conformation of the pheromones was probed using two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) and rotating frame nuclear Overhauer effect spectroscopy (ROESY). The 2D NOE results, and results of complementary one-dimensional experiments, suggest that a type I1 8-turn is assumed by the central portion of active pheromones in both DMSO and water. Inactive analogues of the a-factor do not exhibit this structural feature. Except for this one 8-turn, the nmr parameters for a-factor are indicative of a conformationally flexible molecule in both solvents. This conclusion is in contrast to that of other researchers who have proposed a highly structured conformation of a-factor in aqueous solution.

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Structure-activity relationships in the dodecapeptide .alpha. factor of Saccharomyces cerevisiae

Cited by 37 publications

References 13 publications

Nuclear‐magnetic‐resonance studies on the conformations of tridecapeptide α‐mating factor from yeast Saccharomyces cerevisiae and analog peptides in aqueous solution

Nuclear‐magnetic‐resonance studies on the conformations of tridecapeptide α‐mating factor from yeast Saccharomyces cerevisiae and analog peptides in aqueous solution

Highly Active Analogs of α-Factor and Their Activities Against Saccharomyces cerevisiae

A type II β‐turn in a flexible peptide: Proton assignment and conformational analysis of the α‐factor from saccharomyces cerevisiae in solution

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