The development of glycan-related databases and bioinformatics applications is considerably lagging behind compared with the wealth of available data and software tools in genomics and proteomics. Because the encoding of glycan structures is more complex, most of the bioinformatics approaches cannot be applied to glycan structures. No standard procedures exist where glycan structures found in various species, organs, tissues or cells can be routinely deposited. In this article the concepts of the GLYCOSCIENCES.de portal are described. It is demonstrated how an efficient structure-based cross-linking of various glycan-related data originating from different resources can be accomplished using a single user interface. The structure oriented retrieval options-exact structure, substructure, motif, composition and sugar components-are discussed. The types of available data-references, composition, spatial structures, nuclear magnetic resonance (NMR) shifts (experimental and estimated), theoretically calculated fragments and Protein Database (PDB) entries-are exemplified for Man(3.) The free availability and unrestricted use of glycan-related data is an absolute prerequisite to efficiently share distributed resources. Additionally, there is an urgent need to agree to a generally accepted exchange format as well as to a common software interface. An open access repository for glyco-related experimental data will secure that the loss of primary data will be considerably reduced.

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For protein kinase C (PKC), a family of isoenzymes with serinekhreonine-kinase activity identified as the major cellular receptor for certain skin irritants and tumor promoters, a new pharmacophore model is presented. By structurehctivity relationship studies of naturally occurring and synthetic diterpene esters of the tigliane type (PKC activators) it is demonstrated that in addition to the oxygen at C20 it is the 0-acyl function in position C13 which is critically essential for skin-irritant and tumor-promoting bioactivities rather than other oxygen atoms. This result is confirmed and extended by computer-assisted molecular modeling of tigliane-type and ingenane-type tumor promoters. It is contrasted to certain features attributed to the pharmacophore based upon the recently determined crystallographic structure of the effector-binding domain Cys2 of PKCG complexed with the pseudo-agonist phorbol 13-acetate.Keywords: protein kinase C ; structure/activity relationship ; phorbol ester; ingenol ester; initiatiodpromotion The major receptor of tumor promoters [l] of the mechanistic 12-0-tetradec:anoylphorbol 13-acetate (TPA)-type was identified as protein kinase C (PKC) [2, 31. The enzyme is part of one of the major cellular signal-transduction pathways involved in important cellular processes such as cell differentiation, cell proliferation, modulation of gene expression [4, 51 and biological phenomena such as multiple-drug resistance (MDR) and drug sensitization [6]. PKC is expressed by a gene family coding for phospholipid-dependent serinelthreonine kinases (12 isoenzymes; molecular masses of 60 -80 kDa). Endogenously the enzyme is activated by 1,2-diacyl-sn-glyceroIs (acyl,Gro, e.g. 1 , Fig. 1) released from inositol phospholipid or phospatidylcholine [7, 81 and exogenously by certain skin irritant and tumor-promoting diterpene esters such as TPA (3, Fig. 1 Ahhreviations. 3-T1, 3-0-tetradecanolyingenol; 3-TIA,, 3-0-acetylingenol ; ANPA. 12-0-anthranoylphorbol 13-acetate; APAN, 12-0-acetylphorbol-13-anthrana~ate; d,, single dose of initiator; dp, single dose of promoter; acyl,Gro, 1,2-diacyl-sn-glycero1; Ac2Gro, 1-acetyl-2-acetylglycerol ; DMBA, 7,12-dimethylbenz[a]anthracene; nrtpp, numerical relative tumor promoting; potency ; P, octanol/water partition coefficient; PBU,, 12-0-butyrylphorbol 13-butyrate; PKC, protein kinase C; rtpp, relative tumor promoting potency; TPA, 12-0-tetradecanoylphorbol 13-acetate; TPA,,, 12-0-acetylphorbol 13-acetate.Dedication. This article is dedicated to Prof. Friedrich Marks on the occasion of his 60th birthday and in view of many years of joint scientific engagement in th'e fascinating field of turnor promoters as a category of risk factors for cancer.

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