1.Amino acid sequence of acylphosphatase from porcine skeletal muscle.
Mizuno Y, Yamazaki M, Takasawa T, Kizaki T, Shiokawa H. J Biochem. 1985 Apr;97(4):1135-42.
The amino acid sequence of acylphosphatase from porcine skeletal muscle was determined. It consists of 98 amino acid residues with N-acetylserine at the amino (N)-terminus: Ac-Ser-Thr-Ala-Arg-Pro-Leu-Lys-Ser-Val-Asp-Tyr-Glu-Val-Phe-Gly -Arg-Val-Gln-Gly-Val-Cys-Phe-Arg-Met-Tyr-Thr-Glu-Asp-Glu-Ala-Arg-Lys-Ile -Gly-Val-Val-Gly-Trp-Val-Lys-Asn-Thr-Ser-Lys-Gly-Thr-Val-Thr-Gly-Gln -Val-Gln-Gly-Pro-Glu-Glu-Lys-Val-Asn-Ser-Met-Lys-Ser-Trp-Leu-Ser-Lys -Ile-Gly-Ser-Pro-Ser-Ser-Arg-Ile-Asp-Arg-Thr-Asn-Phe-Ser-Asn-Glu-Lys- Thr-Ile-Ser-Lys-Leu-Glu-Tyr-Ser-Asn-Phe-Ser-Ile-Arg-Tyr-OH. This sequence has three substitutions of amino acid residues, i.e., Thr/Ala, Ile/Val, and Ile/Val at positions 26, 68, and 96, respectively, from that of horse muscle acylphosphatase, formerly the only mammalian acylphosphatase with known sequence.
2.Modification of the structure of a metallopeptide: synthesis and biological evaluation of (111)In-labeled DOTA-conjugated rhenium-cyclized alpha-MSH analogues.
Cheng Z1, Chen J, Miao Y, Owen NK, Quinn TP, Jurisson SS. J Med Chem. 2002 Jul 4;45(14):3048-56.
Rhenium-cyclized CCMSH analogues are novel melanoma-targeting metallopeptides with high tumor uptake, long tumor retention, and low background in normal tissues, which make these metallopeptides an ideal structural motif for designing novel melanoma-targeting agents. ReCCMSH has been derivatized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelate so that it can be labeled with a wide variety of radionuclides for imaging and therapeutic applications. This study involved optimization of the in vivo biological properties of DOTA-ReCCMSH (S), through modification of the structure of the metallopeptide. Several DOTA-ReCCMSH analogues, Ac-Lys(DOTA)-ReCCMSH (4) DOTA-ReCCMSH(Arg(11)) (6), DOTA-ReCCMSH-OH (8), and DOTA-ReCCMSH-Asp-OH (10), were synthesized using solid phase peptide synthesis followed by rhenium cyclization. The IC(50) values of the metallopeptides were determined through competitive binding assays against (125)I-(Tyr(2))-NDP.
3.Solution stability of linear vs. cyclic RGD peptides.
Bogdanowich-Knipp SJ1, Chakrabarti S, Williams TD, Dillman RK, Siahaan TJ. J Pept Res. 1999 May;53(5):530-41.
Arg-Gly-Asp (RGD) peptides contain an aspartic acid residue that is highly susceptible to chemical degradation and leads to the loss of biological activity. Our hypothesis is that cyclization of RGD peptides via disulphide bond linkage can induce structural rigidity, thereby preventing degradation mediated by the aspartic acid residue. In this paper, we compared the solution stability of a linear peptide (Arg-Gly-Asp-Phe-OH; 1) and a cyclic peptide (cyclo-(1, 6)-Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH2; 2) as a function of pH and buffer concentration. The decomposition of both peptides was studied in buffers ranging from pH 2-12 at 50 degrees C. Reversed-phase HPLC was used as the main tool in determining the degradation rates and pathways of both peptides. Fast atom bombardment mass spectrometry (FAB-MS), electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, liquid chromatography-mass spectrometry (LC-MS), and one- and two-dimensional nuclear magnetic resonance spectroscopy (NMR) were used to characterize peptides 1 and 2 and their degradation products.
4.Structure-function studies of peptides inhibiting the ribonucleotide reductase activity of herpes simplex virus type I.
Gaudreau P1, Brazeau P, Richer M, Cormier J, Langlois D, Langelier Y. J Med Chem. 1992 Jan 24;35(2):346-50.
Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex virus (HSV) type I and II ribonucleotide reductase R2 protein and is 15 times more potent than the latter in its in vitro inhibition of HSV-1 reductase activity. Accordingly, a new series of analogues based on this structure was studied in vitro. The replacement of Asp305 by Asn, Glu, Gln, Ser, or Cys; of Asn304 by Gln or Ser; of Ile303 and Val302 by D-Val; and of Tyr298 by Cha induced an important loss of inhibitory potency. The substitution of Asn304 by Asp; of Thr301 by Cys, Ser, or Val; of Gly300 by Ala or Val; of Ala299 by Val; or of Tyr298 by homoPhe, 4'-fluoro-Phe, 4'-chloro-Phe, 3'-iodo-Tyr, Me-Tyr, or For-Trp led to a moderate decrease of the Ac-VZV R2-(298-306) potency.
