Kyotorphin (KTP, H-Tyr-Arg-OH) was covalently bonded with hydrocortisone or estrone to form the corresponding hydrocortisone-21-O-yl-succinyl-Tyr-ArgOH or estrone-3-O-yl-acyl-Tyr-Arg-OH. Their analgesic activities were investigated using the tail flick test. The potency of the two linkers were significantly higher than that of KTP and the mixture of KTP and hydrocortisone or estrone in the CNS and/or the periphery administration.

The synthesis of a series of enantiopure malonaldehyde monocycloacetals is described. Treatment of 8b with L-tryptophan methyl ester, 5-methoxytryptamine, and tryptamine, respectively, in the Pictet-Spengler condensation gave the corresponding enantiomerically pure key precursors 1-3 and 17-21 in only two steps. Using a chiral amino-diol successfully realized the kinetic resolution of racemic carbolines 23 and 24.

The metabolites Ala-Arg-Pro-Ala-OH, Ala-Arg-Pro-OH, Arg-Pro-Ala-Lys-OH and Pro-Ala-Lys-OH were identified by HPLC/ESI/MS from the in vivo blood of Ala-Arg-Pro-Ala-Lys-OH (P6A) received mice. The in vitro incubation of P6A in the blood of mice the same metabolites were also found by use of the Prep LC System. The protective intermediates of these metabolites were prepared via the solution method using the stepwise synthesis in 77.4, 90, 88, and 80% yield, respectively. After deprotection with catalytic hydrogenation the intermediates were converted into the corresponding sequences Arg-Pro-Ala-Lys-OH, Pro-Ala-Lys-OH, Ala-Arg-Pro-Ala-OH, and Ala-Arg-Pro-OH in 90, 95, 85% and 86% yield, respectively. In the thrombolysis in vivo assay the synthetic Ala-Arg-Pro-Ala-OH, and Ala-Arg-Pro-OH exhibited no activity. On the other hand the thrombolytic activity of Arg-Pro-Ala-Lys-OH was comparable to P6A, and an enhanced thrombolytic activity was observed for Pro-Ala-Lys-OH. In the in vitro fibrinolytic lysis tests the approximate results were obtained and an enhanced activity was also observed for Pro-Ala-Lys-OH. In the euglobulin clot lysis time tests P6A, Arg-Pro-Ala-Lys-OH and Pro-Ala-Lys-OH gave significantly shorter time than that given by UK, demonstrating their fast action.

YSL was prepared stepwise from C terminal to N terminal with the side chain un-protective amino acids, Boc-Leu-OMe, Boc-Ser-OH, and Boc-Tyr-OH, as the starting materials in 39.5% total yield (31.2g/per batch). With the side chain un-protective Boc-(3,5-dibromo)-Tyr-OH and HCl

The linkers of estrogen-GHRPs were prepared by the combination of estradiol, estrone, TyrGlyGlyPheLeuOH, and TyrGlyGlyPheLeuOH. Their anti-osteoporosis effect was evaluated by analyzing the data, for instance the weight of the body, femur, femur ash, the content of calcium and phosphor in the femur, the content of calcium and ALP activity in the serum, obtained from the corresponding bioassay in vivo. The results indicated that the anti-osteoporosis potency for estradiol, estrone, TyrGlyGlyPheLeuOH and TyrGlyGlyPheLeuNH2 may be totally enhanced each other via the corresponding linkers.