Structure-Guided, Single-Point Modifications in the Phosphinic Dipeptide Structure Yield Highly Potent and Selective Inhibitors of Neutral Aminopeptidases

Vassiliou, Stamatia; Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata; Nocek, Bogusław; Mulligan, Rory; Joachimiak, Andrzej; Mucha, Artur

doi:10.1021/jm501071f

Title: Structure-Guided, Single-Point Modifications in the Phosphinic Dipeptide Structure Yield Highly Potent and Selective Inhibitors of Neutral Aminopeptidases

Journal Article · Thu Oct 09 00:00:00 EDT 2014 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/jm501071f· OSTI ID:1261141

Vassiliou, Stamatia; Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata; Nocek, Bogusław; Mulligan, Rory; Joachimiak, Andrzej; Mucha, Artur

Seven crystal structures of alanyl aminopeptidase from Neisseria meningitides (the etiological agent of meningitis, NmAPN) complexed with organophosphorus compounds were resolved to determine the optimal inhibitor–enzyme interactions. The enantiomeric phosphonic acid analogs of Leu and hPhe, which correspond to the P1 amino acid residues of well-processed substrates, were used to assess the impact of the absolute configuration and the stereospecific hydrogen bond network formed between the aminophosphonate polar head and the active site residues on the binding affinity. For the hPhe analog, an imperfect stereochemical complementarity could be overcome by incorporating an appropriate P1 side chain. The constitution of P1'-extended structures was rationally designed and the lead, phosphinic dipeptide hPhePψ[CH₂]Phe, was modified in a single position. Introducing a heteroatom/heteroatom-based fragment to either the P1 or P1' residue required new synthetic pathways. The compounds in the refined structure were low nanomolar and subnanomolar inhibitors of N. meningitides, porcine and human APNs, and the reference leucine aminopeptidase (LAP). The unnatural phosphinic dipeptide analogs exhibited a high affinity for monozinc APNs associated with a reasonable selectivity versus dizinc LAP. In conclusion, another set of crystal structures containing the NmAPN dipeptide ligand were used to verify and to confirm the predicted binding modes; furthermore, novel contacts, which were promising for inhibitor development, were identified, including a π–π stacking interaction between a pyridine ring and Tyr372.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Polish National Science Centre (NCN)

Grant/Contract Number:: AC02-06CH11357; GM094585; 2013/09/B/ST5/00090

OSTI ID:: 1261141

Journal Information:: Journal of Medicinal Chemistry, Vol. 57, Issue 19; ISSN 0022-2623

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 43 works

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References (62)

Phosphinic Peptides: Synthetic Approaches and Biochemical Evaluation as Zn-Metalloprotease Inhibitors Yiotakis, A.; Georgiadis, D.; Matziari, M. Current Organic Chemistry, Vol. 8, Issue 12 https://doi.org/10.2174/1385272043370177	journal	August 2004
Phosphinic Acid Compounds in Biochemistry, Biology and Medicine Collinsova, M.; Jiracek, J. Current Medicinal Chemistry, Vol. 7, Issue 6 https://doi.org/10.2174/0929867003374831	journal	June 2000
Remarkable Potential of the α-Aminophosphonate/Phosphinate Structural Motif in Medicinal Chemistry Mucha, Artur; Kafarski, Paweł; Berlicki, Łukasz Journal of Medicinal Chemistry, Vol. 54, Issue 17 https://doi.org/10.1021/jm200587f	journal	September 2011
Development of Highly Potent and Selective Phosphinic Peptide Inhibitors of Zinc Endopeptidase 24-15 Using Combinatorial Chemistry Jirácek, Jirí; Yiotakis, Athanasios; Vincent, Bruno Journal of Biological Chemistry, Vol. 270, Issue 37 https://doi.org/10.1074/jbc.270.37.21701	journal	September 1995
Development of the First Potent and Selective Inhibitor of the Zinc Endopeptidase Neurolysin Using a Systematic Approach Based on Combinatorial Chemistry of Phosphinic Peptides Jiráček, Jiří; Yiotakis, Athanasios; Vincent, Bruno Journal of Biological Chemistry, Vol. 271, Issue 32 https://doi.org/10.1074/jbc.271.32.19606	journal	August 1996
Synthesis and Modifications of Phosphinic Dipeptide Analogues Mucha, Artur Molecules, Vol. 17, Issue 11 https://doi.org/10.3390/molecules171113530	journal	November 2012
Convenient Synthesis and Diversification of Dehydroalaninyl Phosphinic Peptide Analogues Matziari, Magdalini; Georgiadis, Dimitris; Dive, Vincent Organic Letters, Vol. 3, Issue 5 https://doi.org/10.1021/ol0069103	journal	March 2001
Evaluation of P ₁ '-Diversified Phosphinic Peptides Leads to the Development of Highly Selective Inhibitors of MMP-11 Matziari, Magdalini; Beau, Fabrice; Cuniasse, Philippe Journal of Medicinal Chemistry, Vol. 47, Issue 2 https://doi.org/10.1021/jm0308491	journal	December 2003
Active Methylene Phosphinic Peptides: A New Diversification Approach Matziari, Magdalini; Nasopoulou, Magdalini; Yiotakis, Athanasios Organic Letters, Vol. 8, Issue 11 https://doi.org/10.1021/ol060575m	journal	May 2006
Diastereoselective Solution and Multipin-Based Combinatorial Array Synthesis of a Novel Class of Potent Phosphinic Metalloprotease Inhibitors Makaritis, Anastasios; Georgiadis, Dimitris; Dive, Vincent Chemistry - A European Journal, Vol. 9, Issue 9 https://doi.org/10.1002/chem.200204456	journal	May 2003
Phosphinic Tripeptides as Dual Angiotensin-Converting Enzyme C-Domain and Endothelin-Converting Enzyme-1 Inhibitors Jullien, Nicolas; Makritis, Anastasios; Georgiadis, Dimitris Journal of Medicinal Chemistry, Vol. 53, Issue 1 https://doi.org/10.1021/jm9010803	journal	November 2009
A synthetic method for diversification of the P1′ substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1′ binding pockets of leucine aminopeptidases Vassiliou, Stamatia; Xeilari, Metaxia; Yiotakis, Athanasios Bioorganic & Medicinal Chemistry, Vol. 15, Issue 9 https://doi.org/10.1016/j.bmc.2007.02.042	journal	May 2007
Aminopeptidase N Turner, Anthony J. Handbook of Proteolytic Enzymes https://doi.org/10.1016/B978-0-12-382219-2.00079-X	book	January 2013
Alanyl Aminopeptidase (Bacterial-type) Bhosale, Manoj; Bhaskarla, Chetana; Nandi, Dipankar Handbook of Proteolytic Enzymes https://doi.org/10.1016/B978-0-12-382219-2.00094-6	book	January 2013
Leucyl Aminopeptidase (Animal) Sträter, Norbert; Lipscomb, William N. Handbook of Proteolytic Enzymes https://doi.org/10.1016/B978-0-12-382219-2.00330-6	book	January 2013
Leucyl Aminopeptidase (Plant) Walling, Linda L. Handbook of Proteolytic Enzymes https://doi.org/10.1016/B978-0-12-382219-2.00331-8	book	January 2013
Leucyl Aminopeptidase of Plasmodium falciparum Nsangou, Desire M. M.; Mathew, Rency T.; Thivierge, Karine Handbook of Proteolytic Enzymes https://doi.org/10.1016/B978-0-12-382219-2.00333-1	book	January 2013
Leucine aminopeptidases: diversity in structure and function Matsui, Mikiko; Fowler, Jonathan H.; Walling, Linda L. Biological Chemistry, Vol. 387, Issue 12 https://doi.org/10.1515/BC.2006.191	journal	January 2006
Leucine Aminopeptidase as a Target for Inhibitor Design Grembecka, J.; Kafarski, P. Mini-Reviews in Medicinal Chemistry, Vol. 1, Issue 2 https://doi.org/10.2174/1389557013406990	journal	July 2001
The Structure and Main Functions of Aminopeptidase N Luan, Yepeng; Xu, Wenfang Current Medicinal Chemistry, Vol. 14, Issue 6 https://doi.org/10.2174/092986707780059571	journal	March 2007
The moonlighting enzyme CD13: old and new functions to target Mina-Osorio, Paola Trends in Molecular Medicine, Vol. 14, Issue 8 https://doi.org/10.1016/j.molmed.2008.06.003	journal	August 2008
Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects Bauvois, Brigitte; Dauzonne, Daniel Medicinal Research Reviews, Vol. 26, Issue 1 https://doi.org/10.1002/med.20044	journal	January 2005
Aminopeptidase N (APN/CD13) as a Target for Anti-Cancer Agent Design Zhang, Xiaopan; Xu, Wenfang Current Medicinal Chemistry, Vol. 15, Issue 27 https://doi.org/10.2174/092986708786242840	journal	November 2008
Aminopeptidase N (CD13) as a target for cancer chemotherapy Wickström, Malin; Larsson, Rolf; Nygren, Peter Cancer Science, Vol. 102, Issue 3 https://doi.org/10.1111/j.1349-7006.2010.01826.x	journal	January 2011
Positioning of aminopeptidase inhibitors in next generation cancer therapy Hitzerd, Sarina M.; Verbrugge, Sue Ellen; Ossenkoppele, Gert Amino Acids, Vol. 46, Issue 4 https://doi.org/10.1007/s00726-013-1648-0	journal	January 2014
Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials Skinner-Adams, Tina S.; Stack, Colin M.; Trenholme, Katharine R. Trends in Biochemical Sciences, Vol. 35, Issue 1 https://doi.org/10.1016/j.tibs.2009.08.004	journal	January 2010
Metallo-aminopeptidase inhibitors Mucha, Artur; Drag, Marcin; Dalton, John P. Biochimie, Vol. 92, Issue 11 https://doi.org/10.1016/j.biochi.2010.04.026	journal	November 2010
The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity Grembecka, Jolanta; Mucha, Artur; Cierpicki, Tomasz Journal of Medicinal Chemistry, Vol. 46, Issue 13 https://doi.org/10.1021/jm030795v	journal	May 2003
An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling, inhibitory studies and molecular modeling Węglarz-Tomczak, Ewelina; Poręba, Marcin; Byzia, Anna Biochimie, Vol. 95, Issue 2 https://doi.org/10.1016/j.biochi.2012.10.018	journal	February 2013
Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S. PLoS ONE, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pone.0031938	journal	February 2012
α-Aminoalkylphosphonates as a tool in experimental optimisation of P1 side chain shape of potential inhibitors in S1 pocket of leucine- and neutral aminopeptidases Drąg, Marcin; Grembecka, Jolanta; Pawełczak, Małgorzata European Journal of Medicinal Chemistry, Vol. 40, Issue 8 https://doi.org/10.1016/j.ejmech.2005.02.011	journal	August 2005
Synthesis and Structure–Activity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from Plasmodium falciparum Kannan Sivaraman, Komagal; Paiardini, Alessandro; Sieńczyk, Marcin Journal of Medicinal Chemistry, Vol. 56, Issue 12 https://doi.org/10.1021/jm4005972	journal	June 2013
Phosphorus amino acid analogs as inhibitors of leucine aminopeptidase Giannousis, Peter P.; Bartlett, Paul A. Journal of Medicinal Chemistry, Vol. 30, Issue 9 https://doi.org/10.1021/jm00392a014	journal	September 1987
Inhibition of aminopeptidases by aminophosphonates Lejczak, Barbara; Kafarski, Pawel; Zygmunt, Jan Biochemistry, Vol. 28, Issue 8 https://doi.org/10.1021/bi00434a060	journal	April 1989
A highly convenient route to optically pure α-aminophosphonic acids Hamilton, Robert; Walker, Brian; Walker, Brian J. Tetrahedron Letters, Vol. 36, Issue 25 https://doi.org/10.1016/0040-4039(95)00750-7	journal	June 1995
1-Aminoalkylphosphonous acids. Part 1. Isosteres of the protein amino acids Baylis, E. Keith; Campbell, Colin D.; Dingwall, John G. Journal of the Chemical Society, Perkin Transactions 1 https://doi.org/10.1039/p19840002845	journal	January 1984
High-performance liquid chromatographic enantiomer separation and determination of absolute configurations of phosphinic acid analogues of dipeptides and their α-aminophosphinic acid precursors Lämmerhofer, Michael; Hebenstreit, Dieter; Gavioli, Elena Tetrahedron: Asymmetry, Vol. 14, Issue 17 https://doi.org/10.1016/S0957-4166(03)00537-8	journal	September 2003
Crystal structure of aminopeptidase N from human pathogen Neisseria meningitidis Nocek, B.; Mulligan, R.; Bargassa, M. Proteins: Structure, Function, and Bioinformatics, Vol. 70, Issue 1 https://doi.org/10.1002/prot.21276	journal	September 2007
Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site Addlagatta, A.; Gay, L.; Matthews, B. W. Proceedings of the National Academy of Sciences, Vol. 103, Issue 36 https://doi.org/10.1073/pnas.0606167103	journal	August 2006
Structural Basis for the Unusual Specificity of Escherichia coli Aminopeptidase N Addlagatta, Anthony; Gay, Leslie; Matthews, Brian W. Biochemistry, Vol. 47, Issue 19 https://doi.org/10.1021/bi7022333	journal	April 2008
Discovery of α,β- and α,γ-Diamino Acid Scaffolds for the Inhibition of M1 Family Aminopeptidases Gumpena, Rajesh; Kishor, Chandan; Ganji, Roopa Jones ChemMedChem, Vol. 6, Issue 11 https://doi.org/10.1002/cmdc.201100298	journal	August 2011
Transition State Analog L-Leucinephosphonic Acid Bound to Bovine Lens Leucine Aminopeptidase: X-ray Structure at 1.65 .ANG. Resolution in a New Crystal Form Strater, Norbert; Lipscomb, William N. Biochemistry, Vol. 34, Issue 28 https://doi.org/10.1021/bi00028a033	journal	July 1995
Inhibition of the Aminopeptidase from Aeromonas proteolytica by l -Leucinephosphonic Acid. Spectroscopic and Crystallographic Characterization of the Transition State of Peptide Hydrolysis ^† Stamper, Carin; Bennett, Brian; Edwards, Tanya Biochemistry, Vol. 40, Issue 24 https://doi.org/10.1021/bi0100891	journal	June 2001
Zinc Coordination Geometry and Ligand Binding Affinity: The Structural and Kinetic Analysis of the Second-Shell Serine 228 Residue and the Methionine 180 Residue of the Aminopeptidase from Vibrio proteolyticus Ataie, Niloufar J.; Hoang, Quyen Q.; Zahniser, Megan P. D. Biochemistry, Vol. 47, Issue 29 https://doi.org/10.1021/bi702188e	journal	June 2008
Identification of Phosphinate Dipeptide Analog Inhibitors Directed against the Plasmodium falciparum M17 Leucine Aminopeptidase as Lead Antimalarial Compounds Skinner-Adams, Tina S.; Lowther, Jonathan; Teuscher, Franka Journal of Medicinal Chemistry, Vol. 50, Issue 24 https://doi.org/10.1021/jm070733v	journal	November 2007
Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan Proceedings of the National Academy of Sciences, Vol. 106, Issue 8 https://doi.org/10.1073/pnas.0807398106	journal	February 2009
Individual stereoisomers of phosphinic dipeptide inhibitor of leucine aminopeptidase Mucha, Artur; Lämmerhofer, Michael; Lindner, Wolfgang Bioorganic & Medicinal Chemistry Letters, Vol. 18, Issue 5 https://doi.org/10.1016/j.bmcl.2008.01.107	journal	March 2008
Structural basis for multifunctional roles of mammalian aminopeptidase N Chen, L.; Lin, Y. -L.; Peng, G. Proceedings of the National Academy of Sciences, Vol. 109, Issue 44 https://doi.org/10.1073/pnas.1210123109	journal	October 2012
Amidoalkylation of hydrophosphoryl compounds Dmitriev, M. E.; Rossinets, E. A.; Ragulin, V. V. Russian Journal of General Chemistry, Vol. 81, Issue 6 https://doi.org/10.1134/S1070363211060041	journal	June 2011
Shortcut to Fmoc-Protected Phosphinic Pseudodipeptidic Blocks Matziari, Magdalini; Yiotakis, Athanasios Organic Letters, Vol. 7, Issue 18 https://doi.org/10.1021/ol051622y	journal	August 2005
Facile reduction of ethyl thiol esters to aldehydes: application to a total synthesis of (+)-neothramycin A methyl ether Fukuyama, Tohru; Lin, Shao Cheng; Li, Leping Journal of the American Chemical Society, Vol. 112, Issue 19 https://doi.org/10.1021/ja00175a043	journal	September 1990
Reduction of esters of carboxylic acids into aldehydes with diisobutylaluminium hydride Zakharkin, L. I.; Khorlina, I. M. Tetrahedron Letters, Vol. 3, Issue 14 https://doi.org/10.1016/S0040-4039(00)70918-X	journal	June 1962
Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa) Polla, Magnus O.; Tottie, Louise; Nordén, Carita Bioorganic & Medicinal Chemistry, Vol. 12, Issue 5 https://doi.org/10.1016/j.bmc.2003.12.039	journal	March 2004
Design of the first highly potent and selective aminopeptidase N (EC 3.4.11.2) inhibitor Chen, Huixiong; Roques, Bernard P.; Fournié-Zaluski, Marie-Claude Bioorganic & Medicinal Chemistry Letters, Vol. 9, Issue 11, p. 1511-1516 https://doi.org/10.1016/S0960-894X(99)00219-X	journal	June 1999
Phosphinic Derivatives as New Dual Enkephalin-Degrading Enzyme Inhibitors: Synthesis, Biological Properties, and Antinociceptive Activities Chen, Huixiong; Noble, Florence; Mothé, Aurélie Journal of Medicinal Chemistry, Vol. 43, Issue 7 https://doi.org/10.1021/jm990483l	journal	April 2000
α-Aminoalkylphosphonates as a Tool in Experimental Optimisation of P1 Side Chain Shape of Potential Inhibitors in S1 Pocket of Leucine- and Neutral Aminopeptidases. Drag, Marcin; Grembecka, Jolanta; Pawelczak, Malgorzata ChemInform, Vol. 36, Issue 52 https://doi.org/10.1002/chin.200552150	journal	December 2005
Aminopeptidase-N/CD13 (EC 3.4.11.2) Inhibitors: Chemistry, Biological Evaluations, and Therapeutic Prospects Bauvois, Brigitte; Dauzonne, Daniel ChemInform, Vol. 37, Issue 19 https://doi.org/10.1002/chin.200619242	journal	May 2006
On the location of the aminopeptidase N homolog Pf A-M1 in Plasmodium falciparum Klemba, Michael Proceedings of the National Academy of Sciences, Vol. 106, Issue 22 https://doi.org/10.1073/pnas.0903493106	journal	June 2009
Aminopeptidase Fingerprints, an Integrated Approach for Identification of Good Substrates and Optimal Inhibitors Drag, Marcin; Bogyo, Matthew; Ellman, Jonathan A. Journal of Biological Chemistry, Vol. 285, Issue 5 https://doi.org/10.1074/jbc.m109.060418	journal	November 2009
The X-ray Crystal Structure of Human Aminopeptidase N Reveals a Novel Dimer and the Basis for Peptide Processing* Wong, Alan H. M.; Zhou, Dongxia; Rini, James M. Journal of Biological Chemistry, Vol. 287, Issue 44 https://doi.org/10.1074/jbc.m112.398842	journal	October 2012
Crystal Structure of Aminopeptidase N (Proteobacteria Alanyl Aminopeptidase) from Escherichia coli and Conformational Change of Methionine 260 Involved in Substrate Recognition Ito, Kiyoshi; Nakajima, Yoshitaka; Onohara, Yuko Journal of Biological Chemistry, Vol. 281, Issue 44 https://doi.org/10.1074/jbc.m605203200	journal	November 2006
Structure of aminopeptidase N from Escherichia coli complexed with the transition-state analogue aminophosphinic inhibitor PL250 Fournié-Zaluski, Marie-Claude; Poras, Hervé; Roques, Bernard P. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 8 https://doi.org/10.1107/s090744490901779x	journal	July 2009

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