Arg-Gly-Asp-Phe

When H-Cys(Acm)-Arg-Gly-Asp-Phe-Cys(Acm)-NH2, prepared from the same protected peptide resin by HF treatment, was subjected to I2 oxidation in soln, the peptide and other reagents could not be separated, and the desired product was not obtained. 

Addition of the lithium enolate of ethyl acetate to sulfinimine 153 gave 154 with a diastereomeric ratio (d.r.) of 89 11.88 Separation of the diastereoisomers by flash chromatography and deprotection with TFA/EtOH afforded the P-amino ester 155 in >97% ee and 68% overall yield. (S)-Ethyl P-amino-3-pyridinepropanoate (155) is a key component of the peptidomimetic 156 for the Arg-Gly-Asp-Phe sequence of fibrinogen. 

Med. Chem., 35, 4914 (1992). Potent Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp-Phe Sequence of Fibrinogen. A Proposal on the Nature of the Binding Interactions Between the Asp-Carboxylate of RGDX Mimetics and the Platelet GP Ilb/lIIa Recep-... 

Lindmark, S. G. Panzer-Knodle, N. S. Nicholson, B. B. Taite, A. K. Salyers, L. W. King, J. G. Campion, and L. P. Feigen, /. Med. Chem., 36, 1811 (1993). Potent In Vitro and In Vivo Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp-Phe Sequence of Fibrinogen. A Proposal on the Nature of the Binding Interactions Between the Arg-Guanidine of the RGDX Mimetics and the Platelet GP Ilb-IIIa Receptor. 

Hirulog-8 has the formula H-(D-Phe)-Pro-Arg-Pro-(Gly)4-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH. Hirulog-8 was synthesized by conventional solid-phase peptide synthesis employing an Applied Biosystems 430 A Peptide Synthesizer. This peptide was synthesized using BOC-L-Leucine-O-divinylbenzene resin. Additional t-BOC-amino acids (Peninsula Laboratories,... 

Figure 3.18 The Edman degradation. The labeled amino-terminal residue PTH-alanine in the first round) can be released without hydrolyzing the rest of the peptide. Hence, the amino-terminal residue of the shortened peptide (Gly-Asp-Phe-Arg-Gly) can be determined in the second round. Three more rounds of the Edman degradation reveal the complete sequence of the original peptide.

Karl Thomae [82] initially designed pyrollidinone (27) based on the observation that tetrapeptides Arg-Gly-Asp-AA (AA = Ser, Val, Phe) were more potent inhibitors of platelet aggregation than Arg-Gly-Asp alone. They deduced that the tetrapeptides adopted a / or y-turn (illustrated) which pre-... 

Fibrinopeptides the two pairs of peptides (A and B) cleaved from the /V-termini of the 2a and 2P chains of fibrinogen by thrombin. F. arise by cleavage of Arg-GIy bon so that Arg is the C-terminal end of the F, and Gly is the A/-terminal end of the a and P chains of fibrin. Human FA. is Ala-Asp-Ser-Gly-Glu-Gly-Asp-Phe-Leu-Ala-Glu-(Gly)3-Val-Arg, and human F.B. is Pyr-Glu-Gly-Val-Asn-Asp-Asn-(Glu)2-Gly-(Phe)2-Ser-Ala-Arg. F.A. ranges in size from 14 amino acids (horse, lizard) to 19 (cattle), and F.B. from 9 (rhesus monkeys) to 21 (cattle, elk and kangaroo). The sequences of the F. have been used to establish a detailed phylogenetic tree for mammals which is very similar to the classical one. The F. have a vasoconstrictive effect which serves to keep the coagulation principles from being removed too quickly from an injury site. 

FiguraS. HPLC of total crude phosphopeptides. (a) H-Phe-Phe-Lys-Asn-lle-Val-Thr-Pro-Arg-Thr(P03H2)-Pro-Pro-Pro-Ser-Gln-Gly-Lys-NH2. Conditions column Beckman CIS eluant A, 0.1% aq. TFA, eluant B, 0.1% TFA in acetonitrile gradient 0% to 100% B in 40 min flow rate 1 ml/min. (bl H-Gly-Asp-Phe-Glu-Glu-lle-Pro-Glu-Glu-Thr(P03H2)-Leu-NH2. Conditions column TSK-120T eluant A, 0.1% aq. TFA, eluant B, 90% acetonitrile/10% water/0.1% TFA gradient 5% B for 5 min then to 100% in 50 min flow rate 1 ml/min. Opticai density was measured at 214 nm.

---