Re: CCL:W:glycine template isosters



 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
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