Linkage isomerism in the binding of pentapeptide Ac-His(ALA)3His-NH2 to (Ethylenediamine)Palladium(II): Effect of the binding mode on peptide conformation

Hoang, H.N., Bryant, G.K., Kelso, M.J., Beyer, R.L., Appleton, T.G. and Fairlie, D.P. (2008) Linkage isomerism in the binding of pentapeptide Ac-His(ALA)3His-NH2 to (Ethylenediamine)Palladium(II): Effect of the binding mode on peptide conformation. Inorganic Chemistry, 47 20: 9439-9449. doi:10.1021/ic800970p


Author Hoang, H.N.
Bryant, G.K.
Kelso, M.J.
Beyer, R.L.
Appleton, T.G.
Fairlie, D.P.
Title Linkage isomerism in the binding of pentapeptide Ac-His(ALA)3His-NH2 to (Ethylenediamine)Palladium(II): Effect of the binding mode on peptide conformation
Formatted title
Linkage isomerism in the binding of pentapeptide Ac-His(ALA)3His-NH2 to (Ethylenediamine)Palladium(II):   Effect of the binding mode on peptide conformation
Journal name Inorganic Chemistry   Check publisher's open access policy
ISSN 0020-1669
Publication date 2008-09-13
Year available 2008
Sub-type Article (original research)
DOI 10.1021/ic800970p
Open Access Status
Volume 47
Issue 20
Start page 9439
End page 9449
Total pages 11
Place of publication United States
Publisher American Chemical Society
Language eng
Subject C1
030201 Bioinorganic Chemistry
030207 Transition Metal Chemistry
030406 Proteins and Peptides
970103 Expanding Knowledge in the Chemical Sciences
Abstract The reaction of the pentapeptide Ac-His1-Ala2-Ala3-Ala4-His5-NH2 (AcHAAAHNH2) (1) with [Pd(en)(ONO2)(2)] (en = NH2CH2CH2NH2) in either DMF-d(7) or H2O:D2O (90%:10%) gave three linkage isomers of [Pd(en)(AcHAAAHNH2)](2+) (2), 2a, 2b, and 2c, which differ only in which pair of imidazole nitrogen atoms bind to Pd. In the most abundant isomer, 2a, Pd is bound by N1 from each of the two imidazole rings. In the minor isomers 2b and 2c, Pd is bound by N1(His1) and N3(His5) and by N3(His1) and N1(His5), respectively. The reactions of [Pd(en)(ONO2)(2)] with the N-methylated peptides Ac-(N3-MeHis)Ala-Ala-Ala-(N3-MeHis)-NH2 (AcH*AAAH*NH2) (3), Ac-(N3-MeHis)-Ala-Ala-Ala-(N1-MeHis)-NH2 (AcH*AAAH(#)NH(2)) (4), and Ac(N1-MeHis)-Ala-Ala-Ala-(N3-Me-His)-NH2 (AcH(#)AAAH*NH2) (5) each gave a single species [Pd(en)(peptide)](2+) in N,Ndimethylformamide (DMF) or aqueous solution, 7, 8, and 9, respectively, with Pd bound by the two nonmethylated imidazole nitrogen atoms in each case. These complexes were analogous to 2a, 2b, and 2c, respectively. Ac-(N1-MeHis)-Ala-Ala-Ala(N1-MeHis)-NH2 (AcH(#)AAAH(#)NH(2)) (6) with [Pd(en)(ONO2)21 in DMF slowly gave a single product, [Pd(en)(AcH(#)AAAH(#)NH(2))]21 (10), in which Pd was bound by the N3 of each imidazole ring, The corresponding linkage isomer of 2 was not observed. Complex 10 was also the major product in aqueous solution, but other species were also present. All compounds were exhaustively characterized in solution by multinuclear 1D (H-1, C-13, and, with N-15-labeled ethylenediamine, N-15) and 2D (correlation spectroscopy, total correlation spectroscopy, transverse rotating-frame Overhauser effect spectroscopy (T-ROESY), heteronuclear multiplebond correlation, and heteronuclear single quantum coherence) NMR spectra, circular dichroism (CD) spectra, electrospray mass spectroscopy, and reversed-phase high-performance liquid chromatography. ROESY spectra were used to calculate the structure of 2a, which contained a single turn of a peptide alpha helix in both DMF and water, the helix being better defined in DMF The Pd(en)(2+) moiety was not used in structure calculations, but its location and coordination by one imidazole N1 from each histidine to form a 22-membered metallocycle were unambiguously established. Convergence of the structures was greatest when calculated with two hydrogen-bond constraints (Ala4 pepticle NH center dot center dot center dot OC acetyl and His5 peptide NH center dot center dot center dot OC-His1) that were indicated by the low temperature dependence of these NH chemical shifts. Vicinal HN-CH alpha coupling constants and chemical shifts of alpha-H atoms were also consistent with a helical conformation. Similar long-range ROE correlations were observed for [Pd(en)(AcH*AAAH*NH2)](2+) (7), which displayed a CD spectrum in aqueous solution that suggested the presence of some helicity. Long-range ROE correlations were not observed for 8, 9, or 10, but a combination of NMR data and CD spectroscopy was interpreted in terms of the conformational behavior of the coordinated pentapeptide. Only for the linkage isomer [Pd(en)(AcH*AAAH(#)NH(2))](2+) (8) was there evidence of a contribution from a helical conformation.
Keyword Chemistry, Inorganic & Nuclear
Chemistry
CHEMISTRY, INORGANIC & NUCLEAR
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 31 Mar 2009, 18:02:31 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences