Conformationally constrained analogues of endogenous tripeptide inhibitors of zinc metalloproteinases.

Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide inhibitors of snake venom endopeptidases, have been prepared as potential inhibitors of adamalysin II and matrix metalloproteinases. They proved to be inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B, stromelysin 1 and human neutrophil collagenase. Evaluation of the mode of binding of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the decrease of potency may be due to the reorientation of the acylamino chain in three of the heterocyclic nucleus, to a short contact at the entrance of the S'(1) hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus in the P'(1), P'(2) region of the inhibitor, which prevents optimal arrangement in the S'(1) specificity subsite.

Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides.

Phosphonate analogues of the peptidomimetic N-(Furan-2-yl)carbonyl-Leu-Trp-OH were prepared with the goal of evaluating the effect of phosphonate for carboxylate replacement on binding with snake venom metalloproteinases and MMPs. N-(Furan-2-yl)carbonyl-Leu-L-Trp(P)-(OH)2 showed a 75-fold increase of the inhibiting activity against adamalysin II, a snake venom metalloproteinase structurally related to MMPs and TACE. Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors.

[Volumetric growth of the gestational sac: reliability and clinical limits]. / L'accrescimento volumetrico della camera ovulare: affidabilità e limiti clinici.

Thanks to the continuous progress of the ultrasound scanning in obstetrics it is now possible to see the gestation sac already the 5th week of the pregnancy. Aiming to simplify the methods, of the past, the authors suggest the utilisation of a very simple but at the same time extremely accurate methodology to measure the volume of the gestational sac. The comparison between the data which have been obtained with this study and those reported in the literature showed a substantial uniformity, though the results came from different procedure. At the end of the study, the uses of this parameter as well as its application in the solution of that particular problem in the ultrasound diagnosis which is the "blighted ovum" are explained.