From chemistry-request %-% at %-% ccl.net Tue May 3 11:11:53 2005 Received: from mrbusi1.netcologne.de (mrbusi1.netcologne.de [194.8.194.213]) by server.ccl.net (8.13.1/8.13.1) with ESMTP id j43FBkra031579 for ; Tue, 3 May 2005 11:11:47 -0400 Received: from cosmologic.de (xdsl-213-196-220-231.netcologne.de [213.196.220.231]) by mrbusi1.netcologne.de (Postfix) with ESMTP id 3C0C81A0646; Tue, 3 May 2005 17:11:43 +0200 (CEST) Message-ID: <427794B4.4070504 #%# cosmologic.de> Date: Tue, 03 May 2005 17:11:48 +0200 From: Andreas Klamt User-Agent: Mozilla/5.0 (Windows; U; Windows NT 5.1; en-US; rv:1.6b) Gecko/20031205 Thunderbird/0.4 X-Accept-Language: en-us, en MIME-Version: 1.0 To: "Jan, , Pedersen" Cc: chemistry #%# ccl.net Subject: Re: CCL:W:glycine template isosters References: <200504291831.j3TIVwCo019240 #%# server.ccl.net> In-Reply-To: <200504291831.j3TIVwCo019240 #%# server.ccl.net> Content-Type: text/plain; charset=ISO-8859-1; format=flowed Content-Transfer-Encoding: 7bit X-Spam-Status: No, score=0.1 required=5.0 tests=FORGED_RCVD_HELO autolearn=failed version=3.0.3 X-Spam-Checker-Version: SpamAssassin 3.0.3 (2005-04-27) on server.ccl.net Dear Jan, your request met us during the ot phase of the writing a paper on our novel COSMOsim tool for bioisoster similarity screening. We felt tempted to use it as a test case. We have performed a search for compounds similar to Glycine using our latest tool: COSMOsim. In short terms, COSMOsim calculates intermolecular similarity based the sigma profiles of the target and probe molecules. The sigma profile represents the sigma shielding potential distribution of the molecular surface based on DFT-COSMO calculations. We have shown previously that all kinds of physicochemical and biopharmacological properties can be computed directly from such sigma profiles. We are currently preparing an article that describes the COSMOsim method in detail and its general application to bioisosterism. The compounds presented in the list attached are the most similar isosters of glycine which have approximately the same size and electronic surface properties. You will find that some of the known isosteres for the carboxylic acid (tetrazole, phosphinic and boronic acids) and primary amine moieties (secondary amine, hydroxyl). Small variations in the molecular size are also accepted. Moreover, there are very interesting combinations thereof and the cyclic variants that are worth trying. Please note that the search could have benefitted from using the protein-bound conformation which here was not available to us. We hope that these results stimulate your research and would be happy to get feedback on the experimental results. Please find the detailed results under http://www.cosmologic.de/glycine_ccl.zip Best regards Andreas Klamt Marttin Hornig Michael Thormann (Morphochem AG) USmiles SMS similarity NCC(O)=O 1 NC(C)C(O)=O 0.862 O=C1NN=CC1 0.853 NCCC(O)=O 0.827 OC(C1NC1)=O 0.821 O=Cc1[nH]cnc1 0.817 OCn1cncn1 0.813 O=Cc1[nH]ccn1 0.811 OCNC=O 0.805 NCP(O)O 0.804 O=C1NC(=N)NC1 0.804 Oc1nn(ccc1)=O 0.803 CC(=N)NC#N 0.798 NC1CCONC1=O 0.797 CNCC(O)=O 0.792 NOCC(O)=O 0.79 ON=C(C)N 0.789 Cc1[nH]nnn1 0.786 O=C1NN=CC=C1 0.784 N=C2NC(=O)N1CC21 0.784 COC(=O)NN 0.784 OCC(O)=O 0.783 NCCOB(O)O 0.78 NOC(C)C(O)=O 0.776 O=C1NC(=O)C=C1 0.772 OCS(O)=O 0.77 CCC(N)C(O)=O 0.77 OC1C=CC(O1)=O 0.768 COCC(O)=O 0.768 OC(C1C=CCN1)=O 0.766 O=Cc1c[nH]nc1 0.766 O=Cc1c[nH]cn1 0.766 NCCB(O)O 0.765 OC1CNCCC1=O 0.763 OC1=COC=CC1=O 0.762 OCC(O)C=O 0.762 O=Cc1n[nH]cc1 0.761 NCC(F)C(O)=O 0.761 NC(C)(C)C(O)=O 0.76 OC(C1CCCN1)=O 0.759 Nc1nccnn1 0.758 NOCC#N 0.758 OC(=O)c1cncn1C 0.758 Oc1cnncn1 0.757 OCCC#N 0.757 OC1NC(=O)C=C1 0.757 FCC(=O)N 0.757 OC(C1OC1)=O 0.756 OC1=CC=COC1=O 0.754 CC(=O)C(=O)N 0.754 OC(=O)c1cscn1 0.753 NCC=CC(O)=O 0.752 CC1NCC(=O)N1O 0.75 Jan, , Pedersen wrote: >Greetings CCLers, > >A question to all of you. > >I am trying to list possible isosters of the aminoacid motif H2N-C(R)-COOH or of glycine if you wish that formulation. I am not interested in this from a polymer point of view, I am just trying to list species that would have similar properties (in a QM sense) as glycine or as the aminoacid backbone. > >I am looking at a receptor that binds a single aminoacid, and the main interactions are with the "backbone" H2N- and -COOH groups. So I am thinking about which other small functional groups may serve this purpose... > >Does any of you have any pointers to reviews on this subject or a list of possible isosters please join in the discussion. > >Thanks -- Jan > > > >-= This is automatically added to each message by the mailing script =- >To send e-mail to subscribers of CCL put the string CCL: on your Subject: line >and send your message to: CHEMISTRY #%# ccl.net > >Send your subscription/unsubscription requests to: CHEMISTRY-REQUEST #%# ccl.net >HOME Page: http://www.ccl.net | Jobs Page: http://www.ccl.net/jobs > >If your is mail bouncing from ccl.net domain due to spam filters, please >use the Web based form from CCL Home Page >-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ > > > > > > > > > -- ----------------------------------------------------------------------------- Dr. habil. Andreas Klamt COSMOlogic GmbH&CoKG Burscheider Str. 515 51381 Leverkusen, Germany Tel.: +49-2171-73168-1 Fax: +49-2171-73168-9 e-mail: klamt #%# cosmologic.de web: www.cosmologic.de ----------------------------------------------------------------------------- COSMOlogic Your Competent Partner for Computational Chemistry and Fluid Thermodynamics -----------------------------------------------------------------------------