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3[cm-'] = 990 (vs, sheath), 890 (s, cube) (v(V=O,..,)); 745 (s), 615 (vs) (v,,(V-0-V)). 86.36(3), y =76.83(3)", V = 4914(3) lo6 pm3, Z = 2, e,sl.d = 2.57 g cm-'; solution by direct methods, R = 0.083 for 8551 independent reflections (Fo > 4a(Fo)). Some V centers show a transition from distorted squarepyramidal to distorted tetrahedral coordination with an additional longer bond and four show to a lesser extent a disorder of pyramids and distorted tetrahedra. K,(NEt,H), [V,,O,,] 8H,O, also prepared by us, does not show this disorder, but a very strong unresolvable disorder in the cation/ water of crystallization lattice. Further details of the crystal structure investigation are available on request from the Fachinformationszentrum Karlsruhe, Gesellschaft fur wissenschaftlich-technische Information mbH, W-7514 Eggenstein-Leopoldshafen 2 (FRG), on quoting the depository number CSD-55095, the names of the authors, and the journal citation. [4] a) M. T. Pope, A. Miiller, Angew. Chem. 103 (1991) 56; Angew. Chem. Int. Ed. Engl. 30 (1991) 34; b) A. Miiller, M. Penk, R. Rohlfing, E. Krickemeyer, J. Doring, ibid. 102 (1990) 927 and 29 (1990) 926, and references cited therein; c) A. Miiller, J. Doring, H. Bogge, J. Chem. Soc. Chem. Commun. 1991,273. The bond valence sums for the V atoms were calculated using the expression x n t = ~(d(V-0,)/178)-5.15 (cf. I.

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N α‐9‐Fluorenylmethoxycarbonyl‐Nε‐4‐methyltrityl‐lysine, [Fmoc‐Lys(Mtt)‐OH], was prepared in two steps from lysine, in 42% overall yield. The Nε‐Mtt function can be quantitatively removed upon treatment with 1% TFA in dichloromethane or with a 1:2:7 mixture of acetic acid/trifluoroethanol/dichloromethane for 30 min and 1 h at room temperature, respectively. Under these conditions, groups of the tert‐butyl type and peptide ester bonds to TFA‐labile resins, such as the 2‐chlorodiphenylmethyl‐ and the Wang‐resin, remained intact. The utility of the new derivative in peptide synthesis has been exemplified with the synthesis of a cyclic cholecystokinin analog. As an example of further application, five types of lysine cores suitable for the solid‐phase synthesis of one, two or three epitopes containing antigenic peptides or template‐assembled synthetic proteins have been synthesized on Merrifield, Wang and 2‐chlorodiphenylmethyl resin. © Munksgaard 1995.

Cyclic amide-linked angiotension II (ANGII) analogues have been synthesized by novel strategies, in an attempt to test the ring clustering and the charge relay bioactive conformation recently suggested. These analogues were synthesized by connecting side chain amino and carboxyl groups at positions 1 and 8, 2 and 8, 3 and 8, and 3 and 5, N-terminal amino and C-terminal carboxyl groups at positions 1 and 8, 2 and 8, and 4 and 8, and side chain amino to C-terminal carboxyl group at positions 1 and 8. All these analogues were biologically inactive, except for cyclic [Sar1, Asp3, Lys5]ANGII (analogue 10) which had high contractile activity in the rat uterus assay (30% of ANGII) and [Lys1, Tyr(Me)4, Glu8]ANGII (analogue 7) which had weak antagonist activity (PA2 approximately 6). Precyclic linear peptides synthesized using 2-chlorotrityl chloride resin and N alpha-Fmoc-amino acids with suitable side chain protection were obtained in high yield and purity and were readily cyclized with benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate as coupling reagent. Molecular modeling suggests that the ring structure of the potent analogue can be accommodated in the charge relay conformation proposed for ANGII.

S‐4‐methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc‐Cys(Mmt)‐OH by its reaction with Fmoc‐OSu. As compared to the corresponding Fmoc‐Cys(Trt)‐OH, the S‐Mmt‐function was found to be considerably more acid labile. Quantitative S‐Mmt‐removal occurs selectively in the presence of groups of the tert butyl type and S‐Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr1‐somatostatin on 2‐chlorotrityl resin. In this synthesis groups of the Trt‐type were exclusively used for amino acid side‐chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996.

Besides linear solid phase peptide synthesis, segment condensation in solution and chemical ligation, convergent peptide synthesis (CPS) was developed in order to enable the efficient preparation of complex peptides and small proteins. According to this synthetic strategy, solid phase synthesized and suitably protected peptide fragments corresponding to the entire peptide/protein‐sequence are condensed on a solid support or in solution, to the target protein. This review summarizes CPS performed utilizing the mild 9‐fluorenylmethyloxycarbonyl/tbutyloxycarbonyl‐based protecting scheme for the amino acids. © 1999 John Wiley & Sons, Inc. Biopoly 51: 266–278, 1999

Human gene 2 relaxin (RLX) is a member of the insulin superfamily and is a multi-functional factor playing a vital role in pregnancy, aging, fibrosis, cardioprotection, vasodilation, inflammation, and angiogenesis. RLX is currently applied in clinical trials to cure among others acute heart failure, fibrosis, and preeclampsia. The synthesis of RLX by chemical methods is difficult because of the insolubility of its B-chain and the required laborious and low yielding site-directed combination of its A (RLXA) and B (RLXB) chains. We report here that oxidation of the Met(25) residue of RLXB improves its solubility, allowing its effective solid-phase synthesis and application in random interchain combination reactions with RLXA. Linear Met(O)(25)-RLX B-chain (RLXBO) reacts with a mixture of isomers of bicyclic A-chain (bcRLXA) giving exclusively the native interchain combination. Applying this method Met(O)(25)-RLX (RLXO) was obtained in 62% yield and was easily converted to RLX in 78% yield, by reduction with ammonium iodide.