1.Synthesis of N(alpha)-Boc-N(epsilon)-tetrabenzyl-DTPA-L-lysine and N(alpha)-Fmoc-N(epsilon)-tetra-t-butyl-DTPA-L-lysine, building blocks for solid phase synthesis of DTPA-containing peptides.
Davies JS1, Al-Jamri L. J Pept Sci. 2002 Dec;8(12):663-70.
Two building blocks, Boc-Lys(Bn4-DTPA)-OH and Fmoc-Lys(Bu4(t)-DTPA)-OH have been synthesized via the acylation of the epsilon-amino group of N(alpha)-protected lysine, using suitably protected tetra-esters of diethylene triamine pentaacetic acid (DTPA), a ligand with wide application as a chelating agent for complexing metal tons to peptides.
2.Preparation and application of O-amino-serine, Ams, a new building block in chemoselective ligation chemistry.
Spetzler JC1, Hoeg-Jensen T. J Pept Sci. 1999 Dec;5(12):582-92.
The non-codable amino acid O-amino-serine, Ams, has been prepared in both L- and D-forms as the orthogonally protected derivative, Fmoc-Ams(Boc)-OH (1 and 2). This new amino acid derivative is useful for chemoselective ligations. Under acidic conditions and in the presence of all other common amino acid functionalities, the oxyamine function selectively forms oxime linkages with aldehydes. The Ams residue has been incorporated into both ends of the peptide sequence Asp-Leu-Trp-Gln-Lys using standard SPPS. The deprotected peptide has been used for chemical ligation to afford a peptide dimer as well as a glycopeptide. Ams racemization was found to be negligible, as monitored by HPLC separation of Ams dipeptide diastereomers.
3.Novel sst(4)-selective somatostatin (SRIF) agonists. 1. Lead identification using a betide scan.
Rivier J1, Erchegyi J, Hoeger C, Miller C, Low W, Wenger S, Waser B, Schaer JC, Reubi JC. J Med Chem. 2003 Dec 18;46(26):5579-86.
Hypothesizing that structural constraints in somatostatin (SRIF) analogues may result in receptor selectivity, and aiming to characterize the bioactive conformation of somatostatin at each of its five receptors, we carried out an N(beta)-methylated aminoglycine (Agl) scan of the octapeptide H-c[Cys(3)-Phe(6)-Phe(7)-dTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) that is potent at all SRIF receptor subtypes (sst's) but sst(1). We found that H-c[Cys-LAgl(N(beta)Me,benzoyl)-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (4), H-c[Cys-Phe-LAgl(N(beta)Me,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH (6), H-c[Cys-Phe-LAgl(N(beta)Me,benzoyl)-dTrp-Lys-Thr-Phe-Cys]-OH (8), and H-c[DCys-Phe-LAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (10) had high affinity (IC(50) = 14.3, 5.4, 5.2, and 3.4 nM, respectively) and selectivity for sst(4) (>50-fold over the other receptors). The l-configuration at positions 7 and 8 (l(7), l(8)) yields greater sst(4) selectivity than the l(7), d(8) configuration (6 versus 8).
4.Orthogonally protected artificial amino acid as tripod ligand for automated peptide synthesis and labeling with [(99m)Tc(OH(2))(3)(CO)(3)](+).
Shen Y1, Schottelius M, Zelenka K, De Simone M, Pohle K, Kessler H, Wester HJ, Schmutz P, Alberto R. Bioconjug Chem. 2013 Jan 16;24(1):26-35. doi: 10.1021/bc3003327. Epub 2012 Dec 26.
1,2-Diamino-propionic acid (Dap) is a very strong chelator for the [(99m)Tc(CO)(3)](+) core, yielding small and hydrophilic complexes. We prepared the lysine based Dap derivative l-Lys(Dap) in which the ε-NH(2) group was replaced by the tripod through conjugation to its α-carbon. The synthetic strategy produced an orthogonally protected bifunctional chelator (BFC). The -NH(2) group of the α-amino acid portion is Fmoc- and the -NH(2) of Dap are Boc-protected. Fmoc-l-Lys(Dap(Boc)) was either conjugated to the N- and C-terminus of bombesin BBN(7-14) or integrated into the sequence using solid-phase peptide synthesis (SPPS). We also replaced the native lysine in a cyclic RGD peptide with l-Lys(Dap). For all peptides, quantitative labeling with the [(99m)Tc(CO)(3)](+) core at a 10 μM concentration in PBS buffer (pH = 7.4) was achieved. For comparison, the rhenium homologues were prepared from [Re(OH(2))(3)(CO)(3)](+) and Lys(Dap)-BBN(7-14) or cyclo-(RGDyK(Dap)), respectively.
