{"doi":"10.1039/b810306b","title":"In search of small molecules blocking interactions between HIV proteins and intracellularcofactors","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>One of the major obstacles to pursue the discovery of small molecule inhibitors targeting protein–protein interactions is the flat nature of their interface. X-Ray structures have indeed shown that a large part of the interaction area is buried with atoms closely packed together, implying a lack of available cavities for small molecule binding. Yet, it has become clear that some protein–protein interfaces have a well-defined compact area, commonly referred to as a hot spot, that plays a major role in the affinity of the interaction. These hot spots define potential targets for the development of small molecule protein–protein interaction inhibitors (SMPPIIs). In this review we discuss the interactions between viral and hostproteins that have the potential for the future development of SMPPIIs. In light of the current anti-HIV therapy a short overview of protein–protein interactions that may serve as targets for novel drugs is provided. Our hypothesis will exemplify and discuss the interaction between HIV-1integrase and its cellular cofactorLEDGF/p75, which, as evidenced by crystallography and site directed mutagenesis, displays favourable properties needed for the development of interaction inhibitors.</jats:p>\n                  <jats:p/>","journal":"Molecular BioSystems","year":2008,"id":609816,"datarank":0.5289540786924243,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.0,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650680,"name":"Jan De Rijck","orcid":null,"position":1,"is_corresponding":false},{"id":456223,"name":"Frauke Christ","orcid":"0000-0001-9580-3874","position":2,"is_corresponding":false},{"id":456226,"name":"Zeger Debyser","orcid":"0000-0002-3982-1565","position":3,"is_corresponding":false},{"id":1567558,"name":"Katrien Busschots","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"In search of small molecules blocking interactions between HIV proteins and intracellularcofactors","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>One of the major obstacles to pursue the discovery of small molecule inhibitors targeting protein–protein interactions is the flat nature of their interface. X-Ray structures have indeed shown that a large part of the interaction area is buried with atoms closely packed together, implying a lack of available cavities for small molecule binding. Yet, it has become clear that some protein–protein interfaces have a well-defined compact area, commonly referred to as a hot spot, that plays a major role in the affinity of the interaction. These hot spots define potential targets for the development of small molecule protein–protein interaction inhibitors (SMPPIIs). In this review we discuss the interactions between viral and hostproteins that have the potential for the future development of SMPPIIs. In light of the current anti-HIV therapy a short overview of protein–protein interactions that may serve as targets for novel drugs is provided. Our hypothesis will exemplify and discuss the interaction between HIV-1integrase and its cellular cofactorLEDGF/p75, which, as evidenced by crystallography and site directed mutagenesis, displays favourable properties needed for the development of interaction inhibitors.</jats:p>\n                  <jats:p/>","is_dataset_classified":null,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19081927","pmcid":null,"openalex_id":"https://openalex.org/W2133377333","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"201032","title":"TARGETING HIV INTEGRATION CO-FACTORS, TARGETING CELLULAR PROTEINS DURING NUCLEAR IMPORT OR INTEGRATION OF HIV"}],"total_grants":1,"fwci":2.2471,"citation_percentile":0.87460203,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":5},{"year":2014,"count":3},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2018,"count":2},{"year":2020,"count":1},{"year":2022,"count":1}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://zenodo.org/record/3426338","host_type":"repository"},{"url":"https://zenodo.org/record/3426338","host_type":"repository"},{"url":"https://academic.oup.com/molecular-omics/article-pdf/5/1/21/66228317/b810306b.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1039/b810306b","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19081927","host_type":"repository"},{"url":"https://lirias.kuleuven.be/bitstream/123456789/219040/2/In%20search%20%282009%29.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.1039/B810306B","host_type":""},{"url":"https://dx.doi.org/10.1039/b810306b","host_type":""}],"fields_of_study":["HIV/AIDS drug development and treatment","HIV Research and Treatment","Click Chemistry and Applications","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Humans","Protein Binding","HIV Infections","Anti-HIV Agents","Human Immunodeficiency Virus Proteins"],"keywords":["Small molecule","Protein–protein interaction","Human immunodeficiency virus (HIV)","Computational biology","Mutagenesis","Biology","Plasma protein binding","Drug discovery","Binding site","Biophysics","Nanotechnology","Chemistry","Cell biology","Bioinformatics","Biochemistry","Mutation","Materials science","Virology","Anti-HIV Agents","Human Immunodeficiency Virus Proteins","Animals","Humans","HIV Infections","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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