Design of peptides: Crystal and molecular structure of a 3₁₀‐helical peptide N‐Boc‐L‐Phe‐dehydro‐Phe‐L‐Val‐L‐Phe‐dehydro‐Phe‐L‐Val‐Och₃

Abstract

Highly specific peptide structures can be designed by inserting dehydro residues into peptide sequences. The peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val- OCH3, synthesized by conventional procedures, crystallizes from methanol-water mixtures at 4 degrees C in the tetragonal space group P4(3) with cell parameters a = b = 13.829 +/- 0.003 A, c = 27.587 +/- 0.008 A, V = 5275.5 +/- 0.2 A3, Z = 4, dm = 1.152 +/- 0.005 g cm-3, dcal = 1.150 +/- 0.005 g cm-3. The overall residual factor R = 0.084 for 2342 reflections, with 2 theta max = 140 degrees using CuK alpha radiation. The backbone torsion angles are theta 1 = -171(1) degrees, omega 0 = 168(1) degrees, phi 1 = 77(2) degrees, psi 1 = 41(2) degrees, omega 1 = 169(1) degrees, phi 2 = -46(2) degrees, psi 2 = -24(2) degrees, omega 2 = 179(1) degrees, phi 3 = -63(2) degrees, psi 3 = 19(2) degrees, omega 3 = 171(1) degrees, phi 4 = -67(2) degrees, psi 4 = -8(1) degrees, omega 4 = 169(1) degrees, phi 5 = -61(1) degrees, psi 5 = -26(1) degrees, omega 5 = 177(1) degrees, phi 6 = -122(1) degrees, psi 6T = 26(2) degrees. The peptide adopts a 3(10)-helical conformation with three intramolecular hydrogen bonds (i + 3-->i) involving carbonyl oxygen atoms of Phe1, dehydro-Phe2, Val3, and the NH groups of Phe4, dehydro-Phe5, and Val6 with distances of 3.01(1), 2.82(1), and 3.09(2) A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural and conformational properties of (Z)-?-(1-naphthyl)- dehydroalanine residue

“…However, the ⌬ Z Nap residue showed the tendency to form a helical conformation in peptide 2 possessing two ⌬ Z Nap residues, likewise ⌬ Z Phe residues. [47][48][49][50] Conformational energy map computed for Ac-⌬ Z Nap-NMA is shown in Figure 6, which resembles that for Ac-⌬ Z Phe-NMA 31 well. The ⌬ Z Nap residue gave two regions as the stable conformation: one is ( ϳ Ϫ120°, ϳ 20°) corresponding to the (i ϩ 2) residue of type II ␤-turn and the other is ( ϳ Ϫ44°, ϳ Ϫ34°) corresponding to a 3 10 -helix.…”

Chiral interaction in Gly‐capped N‐terminal motif of 310‐helix and domino‐type induction in helix sense

“…[24][25][26][27][43][44][45][46][47][48][49][50][51][52][53][54][55] Introduction of these residues into a target sequence promotes or stabilizes a helical structure (usually, 3 10 -helix). [24][25][26][27][43][44][45][46][47][48][49][50][51][52][53][54][55] Achiral peptides composed mainly of (D Z Phe-Aib) units, including peptide 2, were found to adopt 3 10 -helix in solution [14][15][16][17][18][19] and in crystal states. 56,57 Theoretical study also supports that the (D Z Phe-Aib)-based periodic sequence has a propensity to take a helical form.…”

Effect of the ΔPhe residue configuration on a didehydropeptides conformation: A combined CD and NMR study

“…It has been found that in the solid state a ∆Phe residue of the Z configuration induces β-turns in short sequences [2][3][4][5][6] and a 3 10 -helix in longer ones or peptides with more than one dehydro residue. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19] Similar conformational properties of ∆ Z Phe have been observed in solution by NMR 8,11,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and CD, 18,19,[27][28][29][30][31][32][33][34][35][36]…”