摘要:

AbstractRapid developments in the biotechnology of new proteins, as well as advances in immunology and the development of pharmaceuticals based on inhibitors and antagonists, have led to immense demands for synthetic peptides. Simultaneous preparation of 100–150 completely different peptides, having chain lengths of up to 20 amino acids can nowadays be achieved using multiple synthesis methods. The yields and qualities of the peptides so obtained are high enough to permit reliable in vivo and in vitro screening for biological activities. Moreover, it is possible to optimize synthetic conditions and to carry out comparative studies on the secondary structures and conformational mapping of proteins. Special multiple synthesis methods facilitate the epitope mapping of larger peptides for diagnostic purposes and for the development of vaccines based on a few hundreds of free or rod‐bound peptides that are useful for immunoassays. Multiple methods of peptide synthesis also enable the preparation of so‐called peptide libraries which could comprise hundreds of thousands of peptides, and by which new perspectives for the screening of lead structures will be opened up. Peptide synthesis using a combination of photolabile protecting groups and photolithographic procedures enables the assembling of peptide libraries on small plates for use in miniature immunoassays. Furthermore, lipopeptide‐antigen conjugates allow both the preparation of peptide‐specific and monoclonal antibodies as well as a complete screening of epitopes of B‐, T‐helper and T‐killer cells. Applications in the areas of AIDS diagnosis, the development of vaccines, and screening for the hormone analogues, demonstrate just some of the possibilities that have been opened up by multiple peptide sy

ISSN:0570-0833    

DOI:10.1002/anie.199203673

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractOne of the great mysteries of cell biology remains the mechanism of information transfer, or signaling, through the cytoplasm of the cell. Natural products that inhibit this process offer a unique window into fundamental aspects of cytoplasmic signal transduction, the means by which extracellular molecules influence intracellular events. Thus, natural products chemistry, including organic synthesis, conformational analysis, and methods of structure elucidation, is a powerful tool in the study of cell function. This article traces our understanding of a group of natural products from the finding that they inhibit cytoplasmic signaling to their current recognition as mediators of the interaction between widely distributed protein targets. The emphasis of the discussion is primarily structural. The interactions between the natural‐product ligands and their protein receptors are analyzed at a molecular level in order to shed light on the molecular mechanisms of the biological functions of these compounds. In the process we hope to illustrate the power of chemical analysis as applied to biological systems. Through chemistry we can understand the molecular basis of biological phenomen

ISSN:0570-0833    

DOI:10.1002/anie.199203841

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractThe first homoleptic trimethylsilylmethyl transition‐metal complexes were synthesized about 20 years ago in the research groups of Wilkinson and Lappert, resulting in a significant advance in the understanding of the thermodynamic and kinetic stability of transition‐metal‐carbon σ bonds. The relatively high thermal stability of these bonds provides a dramatic contrast to the Köbrich lithium carbenoids XCH2Li, known for about 30 years and famous for their extraordinarily high reactivity. Both compound classes illustrate that introduction of a heteroatom into an alkyl ligand can have a profound influence on the structure, stability, and reactivity of an alkylmetal compound, opening the possibility of entirely new reactions. Because of their simple and unambiguous structure, α‐ and β‐heteroatom‐substituted transitionmetal compounds containing the unit [MCH2Y] or [MCH2CH2–Y] (where Y is an element from the 4th–7th main groups or groups 14–17, not including C) are particularly suitable for studying effects of the nature of a heteroatom center (neutral/cationic, coordinatively saturated/Lewis basic) on structure, stability, and reactivity as a function of the type of complex, the nature of M, and the number of methylene groups separating M and Y. The diversity of stabilizing and destabilizing influences emanating from the heteroatom center generally produces a broad spectrum of reactivity and stability. This is reflected in an impressive way in homogeneous catalysis, where functionalized alkylmetal compounds arise as intermediates, as well as in the electronic influences of functionalized alkyl ligands, which are determined largely by the nature

ISSN:0570-0833    

DOI:10.1002/anie.199204011

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204221

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204241

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204261

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204301

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204321

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204341

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199204361

出版商:Hüthig&Wepf Verlag    

年代:1992

数据来源: WILEY