Conformation and membrane activity of an analogue of the peptaibol antibiotic trichogin GA IV with a lipophilic amino acid at the N-terminus.

We have synthesized by solution-phase methods two analogues of the 11-residue lipopeptaibol antibiotic trichogin GA IV in which the N-terminal n-octanoyl group is replaced either by an N-acetylated 2-amino-2-methyl-L-undecanoic acid or by an N-acetylated alpha-aminoisobutyric acid. CD, FTIR absorption. and NMR analyses unequivocally show that the main structural features of trichogin GA IV are preserved in these analogues.

Conformational studies of a potent Leu11,D-Trp12-containing lactam-bridged parathyroid hormone-related protein-derived antagonist.

Human parathyroid hormone-related protein (PTHrP) is expressed in various tissues where it acts as an endocrine/paracrine factor involved in cellular growth, differentiation and development of fetal skeleton. As for parathyroid hormone (PTH), which is the hormone responsible for regulation of extracellular calcium homeostasis, the N-terminal 1-34 fragment can reproduce the full spectrum of calciotropic activities inherent in full-length PTH. Truncation of six amino acid residues from the N-terminus of both hormone sequences generates 7-34 fragments which act as weak antagonists.

Structure of sulfur-substituted rhodanese at 1.36 A resolution.

1.36 A resolution X-ray diffraction data have been recorded at 100 K for bovine liver sulfur-substituted rhodanese, using synchrotron radiation. The crystal structure has been refined anisotropically to a final R factor of 0.

Structure of pig plasma retinol-binding protein at 1.65 A resolution.

The crystal structure of pig plasma retinol-binding protein (RBP) has been determined at 1.65 A resolution. The space group is P212121, with a = 45.

Linear and cyclic peptides as substrates for Lyn tyrosine kinase.

Two Tyr residues are supposed to play a crucial role in the regulation of protein tyrosine kinases of the Src family. Autophosphorylation of Src Tyr416 correlates with enzyme activation, while phosphorylation of C-terminal Tyr527 by Csk gives rise to inactive forms of Src kinases. It has previously been demonstrated that the Src-like tyrosine kinase expressed by the oncogene lyn displays a particularly high affinity (Km 20 microm) toward the dimeric linear and cyclic derivatives of the heptapeptide H-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-OH which reproduces the main autophosphorylation site of most of the Src enzymes.

Structure of the trigonal crystal form of bovine annexin IV.

The structure of a trigonal crystal form of N-terminally truncated [des-(1-9)] bovine annexin IV, an annexin variant that exhibits the distinctive property of binding both phospholipids and carbohydrates in a Ca2+-dependent manner, has been determined at 3 A (0.3 nm) resolution -space group: R3; cell parameters: a=b=118.560 (8) A and c=82.

Aggregation and conformational transition in aqueous solution of a bombolitin III analogue containing a photoreactive side-chain group.

The peptide toxin bombolitin III [B(III)], originally isolated from bumblebee venom, has been shown to undergo a concentration-dependent conformational change from a random structure to an alpha-helix induced by aggregation. The aggregation process and the consequent folding results from a delicate balance of electrostatic and hydrophobic interactions. The conformational change is strongly dependent on pH and salt concentration.

Mono- and bicyclic analogs of parathyroid hormone-related protein. 2. Conformational analysis of antagonists by CD, NMR, and distance geometry calculations.

The conformation of the three cyclic antagonist analogs of parathyroid hormone-related protein (PTHrP)-(7-34) [[Lys13,Asp17]PTHrP-(7-34)NH2,[Lys26,Asp30 ]PTHrP-(7-34)NH2,[Lys13,Asp17,Lys26, Asp30]PTHrP-(7-34)NH2] is investigated by CD, NMR, and extensive computer simulations in aqueous solution and a TFE:water mixture. The structural analysis of these peptides, designed to stabilize different regions of the sequence in alpha-helical conformations, is an important step in addressing the correlation between helical content and binding affinity and bioactivity in this hormone-receptor system. Results from CD and NMR spectroscopy of all three analogues in aqueous solution indicate the presence of alpha-helix only in regions containing a 20-membered lactam ring.

Active site structural features for chemically modified forms of rhodanese.

In the course of the reaction catalyzed by rhodanese, the enzyme cycles between two catalytic intermediates, the sulfur-free and the sulfur-substituted (persulfide-containing) forms. The crystal structure of sulfur-free rhodanese, which was prepared in solution and then crystallized, is highly similar to that of sulfur-substituted enzyme. The inactivation of sulfur-free rhodanese with a small molar excess of hydrogen peroxide relies essentially on a modification limited to the active site, consisting of the oxidation of the essential sulfhydryl to sulfenyl group (-S-OH).

Synthesis and conformational analysis of (alpha Me)Leu/Aib model peptides.

We have synthesized by solution methods and fully characterized a variety of (alpha Me)Leu/Aib model peptides to the octapeptide level. A solution conformational analysis was performed by using infrared absorption. 1H nuclear magnetic resonance, and circular dichroism.

Conformational and binding studies on peptides related to domains I and III of calmodulin.

The conformational and ion-binding properties of two peptide fragments of 25 amino acid residues corresponding to the helix-loop sequences of domains I and III of calmodulin (CaM) were investigated by CD and Tb(3+)-mediated fluorescence spectroscopy. Both peptides exhibit very similar ion binding properties either in water or trifluoroethanol (TFE), and do not allow the differentiation of the two domains in the native protein in terms of their binding capacity. An aggregation phenomenon was observed in TFE with increase of the alpha-helical content.

Preferred conformation of peptides from C alpha,alpha- symmetrically disubstituted glycines: aromatic residues.

The conformational preference of C(alpha,alpha-diphenylglycine (D-phi-g) and C(alpha,alpha)-dibenzylglycine (Dbz) residues was assessed in selected derivatives and small peptides by conformational energy computations, ir absorption, 1H-nmr, and x-ray diffraction. Conformational energy computations on the two monopeptides strongly support the view that these C(alpha,alpha)-symmetrically disubstituted glycines are conformationally restricted and that their minimum energy conformation falls in the fully extended (C5) region. The results of the theoretical analyses appear to be in agreement with the solution and crystal-state structural propensities of three derivatives and seven di- and tripeptides.

Structure, solubility and reactivity of peptides. A conformational study of two protected key intermediates from a large-scale synthesis of thymosin alpha 1.

A conformational study of two protected peptide segments, (1-10 and 11-28), spanning the entire sequence of thymosin alpha 1, in solvents of different polarity and capability of forming hydrogen bonds, is reported. By using infrared absorption and circular dichroism techniques the occurrence of the random coil conformation, the self-associated beta-structure, and the alpha-helix (the latter adopted only by the longer peptide) was established. The self-associated species of the two peptide segments were disrupted either by adding increasing amounts of hexamethylphosphoramide or by dilution.

Molecular structure of peptaibol antibiotics: solution conformation and crystal structure of the octapeptide corresponding to the 2-9 sequence of emerimicins III and IV.

The infrared absorption and 1H nuclear magnetic resonance analyses of chloroform solutions of the terminally-blocked segment corresponding to the 2-9 sequence of emerimicins III and IV, -(Aib)3-L-Val-Gly-L-Leu-(Aib)2-, are consistent with the presence of a 3(10)-helical structure of high thermal stability. The crystal structure of the octapeptide, obtained by X-ray diffraction indicates the formation of a right-handed 3(10)-helix, stabilized by six consecutive intramolecular N-H..