Studies on synthesis and molecular dynamics simulation of dendrimers containing amino acids and peptides

A series of poly(ether-amide) dendrimers with amino acids and peptides as the peripheral functional groups was synthesized, and their structures were confirmed by nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometry (ESI-MS) spectrometry. Molecular dynamics simulation of the peptide dendrimers in solution was performed, indicating that, the prior conformations of the dendrimers were atom number dependent, i.e., with the increases of the atom number, the prior conformations were more spherical. Also, the amino acid α-C atom radial distribution indicated that, with larger peripheral groups, more back-folding of the dendrimers occurred. __________ Translated from Acta Chimica Sinica, 2007, 65(1): 21–26 [译自: 化学 通报]     

Iodocyclization/base-induced hydrodeiodination reaction of 5-substituted 4-alkenols. The influence of substituent on the stereoselective pathway

The electrophilic iodocyclization reaction of (Z)- and (E)-5-n-alkylsubstituted 4-alken-1-ols followed by base-induced hydrodeiodination reaction stereoselectively gave, respectively, (Z)- and (E)-alkylidentetrahydrofurans in high yield. Completely different outcomes were observed with (Z)- and (E)-6,6-dimethylhept-4-en-1-ol: their iodocyclization furnished, respectively, threo- and erythro-2-(1-iodo-2,2-dimetylpropyl)tetrahydrofuran with high stereoselectivity. The threo isomer gave clean formation of 6-tert-butyl-3,4-dihydro-2H-pyran by base-induced ring expansion, while erythro isomer underwent a base-induced ring contraction to 1-cyclopropyl-3,3-dimethylbutan-1-one. Moreover, (Z)- and (E)-5-cyclopropylpent-4-en-1-ol underwent a 6-endo-iodocyclization to threo- and erythro-2-cyclopropyl-3-iodotetrahydro-2H-pyran, respectively, that under the same basic treatment, gave two isomeric 6-cyclopropyldihydro-2H-pyrans in a stereoselective fashion.     

Untersuchungen von Reaktionsmechanismen durch Isotopenmarkierung,IX Zum Ringverengungsmechanismus von 1,4-Benzthiazin-2,3-4H-dion

By¹⁴C-labeling it is shown that the ring contraction reaction of 1,4-benzothiazin-2,3-4H-dione (1), leading via benzthiazol-2-carbonic acid (2) finally to benzthiazole (3), proceeds via hydrolytic opening of the thiolactone-bond in1, irrespectively of H⁺ or OH^– catalysis.

     

Characterization of the 310-helix in model peptides by HRMAS NMR spectroscopy

A tetra- and a hepta-homopeptide from the C(alpha)-tetrasubstituted Aib (alpha-aminoisobutyric acid) residue were covalently linked to the POEPOP resin by the fragment-condensation approach. The conformational preferences of the two model peptides were determined for the first time on a solid support by means of high-resolution magic angle spinning NMR spectroscopy. The results obtained indicate that the Aib homopeptides adopt a regular 3(10)-helical structure even when they are covalently bound to a polymeric matrix, and thus confirm the remarkable conformational stability of the peptides rich in this amino acid. An ATR-FTIR spectroscopic investigation, performed in parallel, also confirmed that these polymer-bound peptides do indeed adopt a helical conformation. The results of this study open the possibility to exploit the peptide-resin conjugates based on C(alpha)-tetrasubstituted alpha-amino acids as helpful, structurally organized templates in molecular recognition studies or as catalysts in asymmetric synthesis.     

Synthetic studies toward macrocidins: an RCM approach for the construction of the central cyclic core

The central macrocyclic core of the macrocidins was constructed using RCM as the key reaction. A preliminary investigation dealing with the key reactions, that is, the Dieckmann cyclization and the RCM, revealed that RCM of the β-ketoamide is better than RCM of the corresponding acyltetramic acid.     

毛细管电泳-单链构象多态性分析检测K-ras基因突变

K ras癌基因的点突变在结直肠癌的发生起重要作用。以异丙醇为聚合反应链转移剂,水相法合成 特性粘度为0.70×10-3m3/kg,分子量为6.5×104的低粘度短链线性聚丙烯酰胺。以6%线性聚丙烯酰胺为 筛分介质,分离温度27℃,分离电压9kV为电泳条件,建立了检测K ras基因突变的毛细管电泳 单链构象多 态性方法。利用该方法检测36例结直肠癌患者肿瘤组织,发现12例K ras基因突变。结果表明:该方法具有 快速、高灵敏的优点,为大规模进行结直肠肿瘤的早期诊断提供了可靠方法。     

Toward direct determination of conformations of protein building units from multidimensional NMR experiments. V. NMR chemical shielding analysis of N-formyl-serinamide,a model for polar side-chain containing peptides

Knowledge of chemical shift-structure relationships could greatly facilitate the NMR chemical shift assignment and structure refinement processes that occur during peptide/protein structure determination via NMR spectroscopy. To determine whether such correlations exist for polar side chain containing amino acid residues the serine dipeptide model, For-L-Ser-NH(2), was studied. Using the GIAO-RHF/6-31+G(d) and GIAO-RHF/TZ2P levels of theory the NMR chemical shifts of all hydrogen ((1)H(N), (1)H(alpha), (1)H(beta1), (1)H(beta2)), carbon ((13)C(alpha), (13)C(beta), (13)C') and nitrogen ((15)N) atoms have been computed for all 44 stable conformers of For-L-Ser-NH(2). An attempt was made to establish correlation between chemical shift of each nucleus and the major conformational variables (omega(0), phi, psi, omega(1), chi,(1) and chi(2)). At both levels of theory a linear correlation can be observed between (1)H(alpha)/phi, (13)C(alpha)/phi, and (13)C(alpha)/psi. These results indicate that the backbone and side-chain structures of For-L-Ser-NH(2) have a strong influence on its chemical shifts.     

Novel Hydrogen‐bond Three Dimensional Networks Generated from the Reaction of Metal Nitrate Hydrate (M = Co,Ni) with Ammonium Thiocynate and Bidentate Ligand Piperazine

The reaction of Co(NO₃)₂·6H₂O with two equivalents of PPz (PPz = piperazine hexahydrate) and two equivalents of NH₄SCN in CH₃OH afforded the complex [Co(NCS)₂(PPz)₂(CH₃OH)₂]. The reaction of Ni(NO₃)₂·6H₂O with two equivalents of PPz and four equivalents of NH₄SCN in CH₃OH afforded the complex [Ni(NCS)₄(PPz)₂]. Their IR spectra have been recorded and the structures have been determined. Crystal data for 1 : space group P&1bar;, a = 6.7208(6) Å, b = 8.4310(8) Å, c = 8.5923(8) Å, a = 77.881(2)°, β = 76.342(2)°, γ = 83.936(2)°, V = 461.75(1) ų, Z = 1 with final residuals R1 = 0.0650 and wR2 = 0.1725. Crystal data for 2 : space group P2(1)/n, a = 7.4209(6) Å, b = 11.0231(9) Å, c = 12.317(1) Å, β = 96.642(9)°, V = 1000.9(2) ų, Z = 2 with final residuals R1 = 0.0378 and wR2 = 0.0809. Important NCS—H‐N and O‐H—N(PPz) hydrogen‐bonding interactions in compound 1 and NCS···H‐N hydrogen‐bonding interactions and NCS—SCN interactions in compound 2 play a significant role in aligning the polymer strands in crystalline solids.     

Conformation of receptor-associated PGI2: An investigation by molecular modeling

Summary To elucidate the conformation of receptor-associated prostacyclin (PGI₂), we first performed structure-activity correlation analysis of over 200 PGI₂ analogues and derived from this analysis several crucial features pertaining to structural requirements for PGI₂ activity [Ah-lim Tsai and Kenneth K. Wu, Eicosanoids, 2 (1989) 131–143]. These structural features proved to be useful guidelines for selecting model molecules for further investigations by molecular mechanics. By properly selecting four analogues with either rigid or uniquely oriented -side chain structure for geometric fitting, we succeeded in maximally minimizing the degree of freedom of the carboxylate terminus of PGI₂. We were able to define the spatial relationship among the four critical functional groups, i.e., C1-COOH, C6a-O, C11-OH and C15-OH. More information is needed, however, to define the geometry of the -side chain, particularly for the moiety beyond C15. Nevertheless, results from structure-activity correlation analysis and molecular modeling provide useful information regarding the conformation of receptor-associated PGI₂, which assumes an elongated conformation instead of the traditional hairpin structure.     

Electronic structure and conformation of N-amino-2,5-dimethylpyrrole derivatives and N-formylaniline

From photoelectronic spectroscopy data N-amino-, N-dimethyl-, N-methylphenyl-, and N-methylformylamino-2,5-dimethylpyrrole molecules were found to have an acoplanar-oriented fragment conformation in the gas phase, while N-formylaniline had a planar structure. In aminopyrroles the n-n repulsion energy of unshared pairs exceeded the n-* conjugation energy.A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan 420083. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 602–606, March, 1992.