Tyr Pro Research Articles

Conformational energy calculation on the neurotensin c‐terminal pentapeptide Arg–Pro–Tyr–Ile–Leu OH

AbstractThe conformational behavior of the C‐terminal neurotensin pentapeptide, Arg–Pro–Tyr–Ile–Leu OH [NT(9–13)], was investigated using empirical energy calculations. A special aim was to display the specific contribution of each residue to induce conformations able to interact with biological receptors. Restrictions were then introduced in intramolecular interactions involving the Arg side chain and the terminal COOH group. The stablest conformations include in the order of decreasing stability: a distorted helical form for the C‐terminal tetrapeptide, a (Pro2–Tyr3) β turn I, an α helix, an extended form, and a (Tyr2–Ile3) β turn III, which are energetically rather close (ΔE < 3 kcal/mol). The NT(9–13) peptide appears then as a rather flexible molcule with a noteworthy ability of adaptation to a substrate. Extended forms would be in agreement with a zipper model of interactions with receptors, whereas folded forms involving helices and β, γ turns would support a lock and key model. The specific contribution of side chains, specially those of Tyr and Arg residues as well as the key position of the Pro residue emerge clearly from this study.

ChemInform Abstract: SYNTHESIS OF CORTICOTROPIN PEPTIDES. XIV. THE SYNTHESIS OF TWO OCTADECAPEPTIDES CORRESPONDING TO THE AMINO ACID SEQUENCE 22‐39 OF PORCINE AND HUMAN CORTICOTROPINS

AbstractDie Synthese der Titelverbindungen (Ia) und (Ib) erfolgt ausgehend vom Oktapeptid (II) durch schrittweisen Aufbau nach üblichen Methoden über die Nona‐ (IV) bzw. Dodekapeptide (V) und Kupplung mit dem Hexapeptid (VI).

Synthesis of Corticotropin Peptides. XIV. The Synthesis of Two Octadecapeptides Corresponding to the Amino Acid Sequence 22–39 of Porcine and Human Corticotropins

Abstract The syntheses are described of two octadecapeptides, H–Val–Tyr–Pro–Asn–Gly–Ala–Glu–Asp–Glu–Leu–Ala–Glu–Ala–Phe–Pro–Leu–Glu–Phe–OH (Ip) and H–Val–Tyr–Pro–Asn–Gly–Ala–Glu–Asp–Glu–Ser–Ala–Glu–Ala–Phe–Pro–Leu–Glu–Phe–OH (Ih), corresponding to a tryptic fragment (positions 22–39) of porcine corticotropin (αp-ACTH) and that of human hormone (αh-ACTH), respectively. The porcine pep tide and the corresponding human peptide are prepared simultaneously by an identical synthetic procedure except for the introduction of amino acid residue in position 31. Synthetic peptide Ip is compared with the authentic αp-ACTH (22–39), which has been isolated from a tryptic hydrolysate of natural αp-ACTH, in terms of chemical and physicochemical properties to establish their identity. These data as well as those obtained with human peptide Ih prove the satisfactory synthesis of the two octadecapeptides.

Biochemical studies on ricin D. XVI. Isolation of tryptic peptides from the ile chain of ricin D and the sequences of some tryptic peptides including N- and C-terminal peptides.

Twenty tryptic peptides were isolated from the performic acid-oxidized He chain of ricin D by Dowex 1 × 2 column chromatography followed by paper chromatography. The amino acids contained in these peptides accounted for 218 out of 266 residues in the whole protein. The amino acid sequences of nine peptides were determined by manual liquid phase or automatic solid phase Edman degradation, and N- and C-terminal sequences of the He chain of ricin D were established to be NH2–Ile–Phe–Pro–Lys–Gln–Tyr–Pro–Ile–Ile– and Cys–Ala–Pro–Pro–Pro–Ser–Ser–Gln–Phe, respectively.

Hypothermia and intolerance to cold induced by intracisternal administration of the hypothalamic peptide neurotensin.

NEUROTENSIN is a tridecapeptide (pGlu–Leu–Tyr–Glu–Asn–Lys–Pro–Arg–Arg–Pro–Tyr–Ile–Leu–COOH)1 isolated from bovine hypothalami2. Using a sensitive and specific radio immunoassay, Carraway and Leeman have demonstrated immunoreactive neurotensin in hypothalamic extracts of rat, mouse, rabbit and human tissue3. Intravenous (i.v.) administration of neurotensin to rats has been reported to cause hypotension (minimum effective dose 100 pmol kg−1 = 0.167 µg kg−1), cyanosis (minimum effective dose 1 nmol kg−1 = 1.67 µg kg−1)2, and hyperglycaemia (minimum effective dose 200 pmol kg−1 = 0.33 µg kg−1)4. These effects are not prevented by adrenalectomy or hypophysectomy. The hypotensive effects are not altered by α- or β-adrenergic blockers. Neurotensin also stimulates the contraction of guinea pig ileum while relaxing rat duodenum in vitro. Neurotensin is as potent as bradykinin in its effects on guinea pig ileum and rat duodenum and thus is classified as a kinin2. It increases plasma gonadotropin levels in ovariectomised, oestrogen–progesterone-treated rats after intravenous injection (minimum effective dose 5 nmol kg−1 = 8.4 µg kg−1)5. Intravenous administration of a dose of 3 µg kg−1 to rats produces hypoinsulinaemia, hyperglycaemia and hyperglucagonaemia6.