Note: AMINO ACIDS, PEPTIDES AND PROTEINS -- Contents -- Chapter 1 Amino Acids -- 1 Introduction -- 2 Textbooks and Reviews -- 3 Naturally Occurring Amino Acids -- 3.1 Isolation of Amino Acids from Natural Sources -- 3.2 Occurrence of Known Amino Acids -- 3.3 New Naturally Occurring Amino Acids -- 3.4 New Amino Acids from Hydrolysates -- 4 Chemical Synthesis and Resolution of Amino Acids -- 4.1 General Methods for the Synthesis of α-Amino Acids -- 4.2 Asymmetric Synthesis of α-Amino Acids -- 4.3 Synthesis of Protein Amino Acids and other Naturally Occurring α-Amino Acids -- 4.4 Synthesis of α-Alkyl Analogues of Protein Amino Acids -- 4.5 Synthesis of α-Amino Acids Carrying Alkyl Side-Chains, and Cyclic Analogues -- 4.6 Models for Prebiotic Synthesis of Amino Acids -- 4.7 Synthesis of α-Alkoxy α-Amino Acids and Analogous α-Hetero-atom Substituted α-Amino Acids -- 4.8 Synthesis of α-(ω-Halogenoalkyl) α-Amino Acids -- 4.9 Synthesis of α-(ω-Halogenoalkyl)-α-Amino Acids -- 4.10 Synthesis of N-Substituted α-Amino Acids -- 4.11 Synthesis of α-Amino Acids Carrying Unsaturated Aliphatic Side-Chains -- 4.12 Synthesis of α-Amino Acids with Aromatic or Heteroaromatic Groupings in Side-Chains -- 4.13 Synthesis of α-(N-Hydroxyamino) Acids -- 4.14 Synthesis of α-Amino Acids Carrying α-(ω-Aminoalkyl) Groups, and Related Nitrogen Functional Groups, in Side-Chains -- 4.15 Synthesis of α-Amino Acids Carrying Sulfur- or Selenium-Containing Side-Chains -- 4.16 Synthesis of α-Amino Acids Carrying Phosphorus Functional Groups in Side-Chains, and α-Amino Phosphonic Acids -- 4.17 Synthesis of α-Amino Acids Carrying Boron Functional Groups in Side-Chains, and α-Amino Boronic Acids -- 4.18 Synthesis of α-Amino Acids with Silicon Functional Groups in Side-Chains -- 4.19 Synthesis of Isotopically Labelled α-Amino Acids. , 4.20 Synthesis of β-Amino Acids and Higher Homologous Amino Acids -- 4.21 Resolution of DL-Amino Acids -- 5 Physico-Chemical Studies of Amino Acids -- 5.1 X-Ray Crystal Analysis of Amino Acids and Their Derivatives -- 5.2 Nuclear Magnetic Resonance Spectroscopy -- 5.3 Optical Rotatory Dispersion and Circular Dichroism -- 5.4 Mass Spectrometry -- 5.5 Other Spectroscopic Studies of Amino Acids -- 5.6 Physico-Chemical Studies of Amino Acids -- 5.7 Molecular Orbital Calculations for Amino Acids -- 6 Chemical Studies of Amino Acids -- 6.1 Racemization -- 6.2 General Reactions of Amino Acids -- 6.3 Specific Reactions of Amino Acids -- 6.4 Effects of Electromagnetic Radiation on Amino Acids -- 7 Analytical Methods -- 7.1 Introduction -- 7.2 Gas-Liquid Chromatography -- 7.3 Ion-Exchange Chromatography -- 7.4 Thin-Layer Chromatography -- 7.5 High Performance Liquid Chromatography -- 7.6 Fluorimetric Analysis -- 7.7 Capillary Zone Electrophoresis, and Other Analytical Methods -- 7.8 Assays for Specific Amino Acids -- References -- Chapter 2 Peptide Synthesis -- 1 Introduction -- 2 Methods -- 2.1 Amino-group Protection -- 2.2 Carboxyl-group Protection -- 2.3 Side-chain Protection -- 2.4 Disulfide Bond Formation -- 2.5 Peptide Bond Formation -- 2.6 Solid-phase Peptide Synthesis -- 2.7 Enzyme-mediated Synthesis and Semi-synthesis -- 2.8 Miscellaneous Reactions Related to Peptide Synthesis -- 3 Appendix: A List of Syntheses Reported in 1995 -- 3.1 Natural Peptides, Proteins, and Partial Sequences -- 3.2 Sequential Oligo- and Poly-peptides -- 3.3 Enzyme Substrates and Inhibitors -- 3.4 Conformation of Synthetic Peptides -- 3.5 Glycopeptides -- 3.6 Phosphopeptides and Related Compounds -- 3.7 Immunogenic Peptides -- 3.8 Nucleopeptides -- 3.9 Miscellaneous Peptides -- 3.10 Purification Methods -- References. , Chapter 3 Analogue and Conformational Studies on Peptide Hormones and Other Biologically Active Peptides -- 1 Introduction -- 2 Peptide-backbone Modifications -- 2.1 ψ[NHCO]-Retro-inversoA nalogues -- 2.2 ψ[CH2NH]-Aminomethylenaen and ψ[CH2O]-Ether Analogues -- 2.3 ψ[CH=CH] Isosteres and Related Analogues -- 2.4 Phosphorus Containing Peptide Bond Isosteres -- 2.5 Sulfur Containing Peptide Bond Isosteres -- 2.6 Aldehyde and Ketone Containing Isosteres -- 2.7 α,α-Dialkylated Glycine Analogues -- 2.8 Dehydroamino Acid Analogues -- 2.9 Miscellaneous -- 3 Conformationally Restricted Cyclic and Bridged Analogues -- 3.1 Rings and Bridges Formed via Amide Bonds -- 3.2 Bridges Formed by Disulfide Bonds -- 3.3 Helices and Helix Inducers -- 3.4 β-Turn Mimetics and Miscellaneous Bridges -- 4 Amino Acids with Modified Side-chains, including Sidechain to Backbone Cyclisations -- 5 Enzyme Inhibitors -- 5.1 Renin Inhibitors -- 5.2 HIV-1 Protease Inhibitors -- 5.3 Inhibitors of Other Protease Enzymes -- 5.3.1 Serine Protease Inhibitors -- 5.3.2 Cysteine Protease Inhibitors -- 5.3.3 Metallo protease Inhibitors -- 5.4 RGD Containing Peptides -- 5.5 Miscellaneous Enzyme Inhibitors -- 6 Side Chain Interactions Studied by Residue Substitution or Deletion and Similar Modifications -- 6.1 Peptides with Opioid Characteristics -- 6.2 Neuropeptide Analogues -- 6.3 Angiotensin Analogues -- 6.4 Oxytocin and Vasopressin Analogues -- 6.5 Thrombin Binding Peptides -- 6.6 Tachykinin Analogues -- 6.7 Somatostatin Analogues -- 6.8 Bradikinin Analogues -- 6.9 Miscellaneous Examples -- References -- Chapter 4 Cyclic, Modified and Conjugated Peptides -- 1 Introduction -- 2 Cyclic Peptides -- 2.1 General Considerations -- 2.2 Dioxopiperazines (Cyclic Dipeptides) -- 2.3 Cyclotripeptides -- 2.4 Cyclotetrapeptides -- 2.5 Cyclopentapeptides -- 2.6 Cyclohexapeptides -- 2.7 Cycloheptapeptides. , 2.8 Cyclooctapeptides -- 2.9 Cyclononapeptides and Cyclodecapeptides -- 2.10 Cyclododeca- and Cyclotetradecapeptides -- 2.11 Higher Cyclic Peptides -- 2.12 Peptides Containing Thiazole/Oxazole Rings -- 2.13 Cyclodepsipeptides -- 3 Modified and Conjugated Peptides -- 3.1 Phosphopeptides -- 3.2 G1 ycopeptide Antibiotics -- 3.3 Glycopeptides -- 3.4 Lipopeptides -- 3.5 Miscellaneous Conjugates -- 4 Miscellaneous Structures -- References -- Chapter 5 β-Lactam Chemistry -- 1 Introduction -- 2 New Natural Products -- 3 Biosynthesis -- 3.1 Penicillin and Cephalosporin Biosynthesis -- 3.1.1 Early Stages -- 3.1.2 ACV Synthetase and Related Enzymes -- 3.1.3 Isopenicillin N Synthase -- 3.1.4 Cephalosporin Biosynthesis -- 3.1.5 Penicillin Acylases -- 3.1.6 Cephalosporin Acylases/Acyltransferases -- 3.2 Clavam Biosynthesis -- 3.3 Carbapenem Biosynthesis -- 3.4 Regulatory and Related Studies -- 4 Penicillins and Cephalosporins -- 5 Carbacephems -- 6 Penems -- 7 Carbapenems, Carbapenams, Carbacephems and Related Systems -- 8 Azetidinones -- 8.1 Synthesis of Azetidinones -- 8.2 Chemistry of Azetidinones -- 8.2.1 N-Chemistry -- 8.2.2 C-2 and C-2' Chemistry -- 8.2.3 C-3 and C-3' Chemistry -- 8.2.4 C-4 and C-4' Chemistry -- 8.2.5 Miscellaneous Reactions of Azetidinones -- 8.3 Further Use of Azetidinones -- 9 Major Structural Variants -- 10 Mechanistic Studies -- 11 New Applications -- Appendix A: Review Articles -- Appendix B: Additional Articles -- References -- Chapter 6 Current Trends in Protein Research -- 1 Introduction -- 2 Protein Folding -- 2.1 New Methods -- 2.2 Protein Folding and Disease -- 2.3 Chaperons -- 2.4 Protein Sequence Motifs and Comparisons -- 3 Proteins that Bind RNA -- 3.1 RNP Domain -- 3.2 Double Stranded RNA Binding Domain -- 3.3 KH Domain -- 3.4 Sm Protein Motif -- 3.5 TRAP Protein -- 3.6 RNA/Protein Complexes -- 4 DNA Binding Proteins. , 4.1 Homeodomain Proteins -- 4.2 Retroviral Integrases -- 4.3 Rel Transcription Factors -- 4.4 BamHI Endonuclease/DNA Complex -- 4.5 Other Protein/DNA complexes -- 4.5.1 ETSI, DNA Binding Domain/DNA Complex -- 4.5.2 Gp32 (Bacteriophage T4)/DNA Complex -- 4.5.3 Lymphoid Enhancer-Binding Factor, HMG Domain, DNA Complex -- 4.5.4 γδ Resolvase/DNA Complex -- 4.5.5 9-cis-Retinoic Acid Receptor α, DNA Binding Domain/Thyroid Hormone Receptor, DNA Binding Domain/DNA Thyroid-response Element Complex -- 4.5.6 Serum Response Factor Core Domain/DNA Complex -- 4.5.7 SRY Protein, DNA Binding Domain/DNA Complex -- 4.5.8 TF1lB/TATA Box Binding Protein/TATA Element Ternary Complex -- 4.6 Exonuclease III -- 4.7 Gal6 Bleomycin Hydrolase -- 5 Metalloenzymes -- 5.1 Heme Protein-Cytochrome cd1 -- 5.2 Chloroperoxidase -- 5.3 Haemopexin -- 5.4 Dihydroxybiphenyl 1,2-Dioxygenase -- 5.5 Sulfite Reductase -- 5.6 Purple Acid Phosphatase -- 5.7 Nickel-containing Enzymes -- 5.7.1 Nickel-Iron Dehydrogenase -- 5.7.2 Urease -- 5.8 Zinc-containing Enzymes -- 5.8.1 Phosphotriesterase -- 5.8.2 RING-Finger -- 5.8.3 Collagenase -- 5.9 Tungsten-containing Protein -- 5.9.1 Aldehyde Ferredoxin Oxidoreductase -- 5.10 Molybdenum-containing Protein -- 5.10.1 Aldehyde Oxidoreductase -- 5.11 Copper-containing Proteins -- 5.11.1 Nitrite Reductase -- 5.11.2 Amine Oxidase -- 5.12 Manganese-containing Proteins -- 5.12.1 Isopenicillin N-Synthase -- 6 Other Protein Structures -- 6.1 Enolase -- 6.2 Cholesterol Esterase -- 6.3 Estrogenic 17β-Hydroxysteroid Dehydrogenase -- 6.4 Enoyl Acyl Carrier Protein Reductase -- 6.5 Pyruvate Kinase -- 6.6 Glucosamine 6-Phosphate Deaminase -- 6.7 Fructose 1,6-Bisphosphatase -- 6.8 Bacterial Sialidase -- 6.9 Influenza Virus Neuraminidase -- 6.10 Glycosyl Hydrolases -- 6.11 Proteins that Bind Co-enzyme A -- 6.12 14-3-3 Proteins -- 6.13 D-Amino Acid Aminotransferase. , 6.14 Aspartylglucosaminidase.

Note: AMINO ACIDS, PEPTIDES AND PROTEINS -- Contents -- Chapter 1 Amino Acids -- 1 Introduction -- 2 Textbooks and Reviews -- 3 Naturally Occurring Amino Acids -- 3.1 Occurrence of Known Amino Acids -- 3.2 New Naturally Occurring Amino Acids -- 3.3 New Amino Acids from Hydrolysates -- 4 Chemical Synthesis and Resolution of Amino Acids -- 4.1 General Methods for the Synthesis of α-Amino Acids including Enan tiostereoselective Synthesis -- 4.1.1 Amination of Alkanoic Acid Derivatives by Amines and Amine-related Reagents -- 4.1.2 Carboxylation of Alkylamines and Imines, and Related Methods -- 4.1.3 Use of Chiral Auxiliaries in Amino Acid Synthesis -- 4.1.4 Use of Rearrangements Generating a Carbon-Nitrogen Bond -- 4.1.5 Other Rearrangments -- 4.1.6 Amidocarbonylation and Related Processes -- 4.1.7 From Glycine Derivatives -- 4.1.8 From 'Dehydro-amino Acid' Derivatives -- 4.2 Synthesis of Protein Amino Acids and Other Naturally Occurring a-Amino Acids -- 4.3 Synthesis of α-Alkyl-α-Amino Acids -- 4.4 Synthesis of α-Amino Acids Carrying Alkyl Side-chains, and Cyclic Analogues -- 4.5 Models for Prebiotic Synthesis of Amino Acids -- 4.6 Synthesis of α-(ω-Halogeno-alky1)-α-Amino Acids -- 4.7 Synthesis of α-(ω-Hydroxyalky1)-α-Amino Acids -- 4.8 Synthesis of N-substituted α-Amino Acids -- 4.9 Synthesis of α-Amino Acids Carrying Unsaturated Aliphatic Side-chains -- 4.10 Synthesis of α-Amino Acids with Aromatic or Heteroiiromatic Groupings in Side-chains -- 4.11 Synthesis of α-Amino Acids Carrying Amino Groups, and Related Nitrogen Functional Groups, in Aliphatic Side-chains -- 4.12 Synthesis of α-Amino Acids Carrying Sulfur-, Selenium-, or Tellurium-containing Side-chains -- 4.13 Synthesis of α-Amino Acids Carrying Silicon Functional Groups in Side-chains -- 4.14 Synthesis of α-Amino Acids Carrying Phosphorus Functional Groups in Side-chains. , 4.15 Synthesis of β-Amino Acids and Higher Homologous Amino Acids -- 4.16 Resolution of DL-Amino Acids -- 5 Physico-chemical Studies of Amino Acids -- 5.1 X-Ray Crystal Analysis of Amino Acids and their Derivatives -- 5.2 Nuclear Magnetic Resonance Spectrometry -- 5.3 Opitical Rotatory Dispersion and Circular Dichroism -- 5.4 Mass Spectrometry -- 5.5 Other Spectroscopic Studies of Amino Acids -- 5.6 Other Physico-chemical Studies of Amino Acids -- 5.6.1 Measurements for Amino Acid Solutions -- 5.6.2 Measurements for Solid Amino Acids -- 5.6.3 Amino Acid Adsorption and Transport Phenomena -- 5.6.4 Host-Guest Studies with Amino Acids -- 5.7 Molecular Orbital Calculations for Amino Acids -- 6 Chemical Studies of Amino Acids -- 6.1 Racemization -- 6.2 General Reactions of Amino Acids -- 6.2.1 Thermal Stability of Amino Acids -- 6.2.2 Reactions at the Amino Group -- 6.2.3 Reactions at the Carboxy Group -- 6.2.4 Reactions at Both Amino and Carboxy Groups -- 6.2.5 Reactions at the α-Carbon Atom of α- and β-Amino Acids -- 6.3 Specific: Reactions of Amino Acids -- 6.4 Effects of Electromagnetic Readiation on Amino Acids -- 7 Analytical Methods -- 7.1 Introduction -- 7.2 Gas-liquid Chromatography -- 7.3 Ion-exchange Chromatography -- 7.4 Thin-layer Chromatography -- 7.5 High-performance Liquid Chromatography -- 7.6 Capillary Zone Electrophoresis (CZE) and Related Analytical Methods -- 7.7 Assays for Specific Amino Acids -- References -- Chapter 2 Peptide Synthesis -- 1 Introduction -- 2 Methods -- 2.1 Amino-group Protection -- 2.2 Carboxy-group Protection -- 2.3 Side-chain Protection -- 2.4 Disulfide Bond Formation -- 2.5 Peptide Bond Formation -- 2.6 Peptide Synthesis on Macromolecular Supports and Methods of Combinatorial Synthesis -- 2.7 Enzyme-mediated Synthesis and Semi-synthesis -- 2.8 Miscellaneous Reactions Related to Peptide Synthesis. , 3 Appendix: A List of Syntheses Reported Mainly in 1997 -- 3.1 Natural Peptides, Proteins and Partial Sequences -- 3.2 Sequential Oligo- and Poly-peptides -- 3.3 Enzyme Substrates and Inhibitors -- 3.4 Conformation of Synthetic Peptides -- 3.5 Glycopeptides -- 3.6 Phosphopeptides and Related Compounds -- 3.7 Immunogenic Peptides -- 3.8 Nucleopeptides -- 3.9 Miscellaneous Peptides -- 3.10 Purification Methods -- References -- Chapter 3 Analogue and Conformational Studies on Peptides, Hormones and Other Biologically Active Peptides -- 1 Introduction -- 2 Peptide Backbone Modifications and Di- and Tri-peptide Mimetics -- 2.1 ψ[CH2WH]-Aminomethylene Analogues -- 2.2 ψ[CH=GH]-Isosteres -- 2.3 ψ[COCH2]-Ketomethylene Isosteres -- 2.4 Retro- and Retro-inverso Psuedopeptides -- 2.5 Rigid Di- and Tri-peptide and Turn Mimetics -- 3 Cyclic Peptides -- 3.1 Naturally Occurring Cyclic Peptides, Synthetic Analogues and Conformational Studies -- 4 Biologically Active Peptides -- 4.1 Peptides Involved in Alzheimer's Disease -- 4.2 Antimicrobial Peptides -- 4.2.1 Antimicrobial Peptides -- 4.2.2 Antifungal Peptides -- 4.3 ACTH/CRF Peptides -- 4.4 Angiotensin I I Analogues and Non-peptide Angiotensin I1 Receptor Ligands -- 4.5 Bombesin/Neuromedin Analogues -- 4.6 Bradykinin Analogues -- 4.7 Cholecy stokinin Analogues -- 4.8 Complement-related Peptide/Non-peptide Analogues -- 4.9 Endothelin Analogues -- 4.10 Growth Hormone-releasing Peptide and Non-peptide Analogues -- 4.1 1 Integrin-related Peptide and Non-peptide Analogues -- 4.12 LHRH Analogues -- 4.13 α-MSH Analogues -- 4.14 Neuropeptide Y (NPY) Analogues -- 4.15 Neurotensin Analogues -- 4.16 Opioid (Enkephalin, β-Casomorphin, Morphiceptin, Deltorphin and Dynorphin) Peptides -- 4.17 Somatostatin Analogues -- 4.18 Tachykinin (Substance P and Neurokinins) Analogues -- 4.19 Thyrotropin-releasing Hormone Analogues. , 4.20 Vasopressin and Oxytocin Analogues -- 5 Enzyme Inhibitors -- 5.1 Calpain Inhibitors -- 5.2 Caspase Inhibitors -- 5.3 Cathepsin Inhibitors -- 5.4 Cytome,galovirus Protease Inhibitors -- 5.5 Converting Enzyme [Angiotensin (ACE), Neutral Endopeptidase (NEP), Endothelin (ECE) and Interleukin-1 p (ICE)] Inhibitors -- 5.5.1 Angiotensin Converting Enzyme and Neutral Endopeptidase Inhibitors -- 5.5.2 Endothelin Converting Enzyme Inhibitors -- 5.5.3 Interleukin 1 β Converting Enzyme Inhibitors -- 5.6 Elastase Inhibitors -- 5.7 Farnesyltransferase Inhibitors -- 5.8 HIV Protease Inhibitors -- 5.9 Matrix Metalloproteinase Inhibitors -- 5.10 Phosphate Inhibitors (Ser/Thr or Tyr) -- 5.11 Renin Inhibitors -- 5.12 Thrombin Inhibitors (Serine Protease) -- 5.13 Miscellaneous [p60c-src Protein Tyrosine Kinase, Serine Proteases (Trypsin and Chymotrypsin), Papain and Prolyl Endopeptidase] Inhibitors -- 6 Phage Library Leads -- 6.1 Erythropoietin and Thrombopoietin Mimetics -- 6.2 Angiogenin and Interleukin Antagonists and Epidermal Growth Factor Receptor Ligands -- 6.3 Enzyme Substrates and Inhibitors [Tissue-type Plasminogen Activator and Urokinase-type Plasminogen Activator Inhibitors, Protein Tyrosine Kinase Substrates and Inhibitors and Calmodulin Kinase Inhibitors] -- 6.4 Protein-Protein tnteraction Inhibitors [Vinculin Binding Peptides and mdm2 Binding Peptides] -- 6.5 Brain and Tumour Targeting of Peptides -- 6.6 Epitope Mapping [Human Galactin-3 Epitopes and Antigenic Epitopes of Streptokinase] -- 6.7 Ion Channel Receptor Binding Peptides -- 6.8 NMR Studies of Phage Peptides -- 7 Protein-Protein Interaction Inhibitors -- 7.1 Inhibitors of Fas and FAP-1 Interaction -- 7.2 Inhibitors of Bcl2-Bax (and Other Members of this Family) Interaction -- 7.3 SH2 Domain Ligands -- 7.4 CD4 Interaction Inhibitors -- 8 Advances in Formulation/Delivery Technology. , 9 Other Peptides (from Insects, Molluscs etc.) -- References -- Chapter 4 Cyclic, Modified and Conjugated Peptides -- 1 Introduction -- 2 Cyclic Peptides -- 2.1 General Considerations -- 2.2 Dioxopiperazines (Cyclic Dipeptides) -- 2.3 Cyclotripeptides -- 2.4 Cyclotetrapeptides -- 2.5 Cyclopentapeptides -- 2.6 Cyclohexapeptides -- 2.7 Cycloheptapeptides -- 2.8 Cyclooctapeptides -- 2.9 Cyclononapeptides -- 2.10 Cyclodecapeptides -- 2.11 Cycloundecapeptides -- 2.12 Cyclododecapeptides -- 2.13 Peptides Containing Thiazole/Oxazole Rings -- 2.14 Cyclodepsipeptides -- 3 Modified and Conjugated Peptides -- 3.1 Phophopeptides -- 3.2 Glycopep tide Antibiotics -- 3.3 Glycopeptides -- 3.3.1 0-Glycopeptides -- 3.3.2 N-Glycopeptides -- 3.3.3 Other Linked Sugars -- 3.4 Lipopeptides -- 4 Miscellaneous Structures -- References -- Chapter 5 P-Lactan Chemistry -- 1 Introduction -- 2 Biosynthesis -- 2.1 Early Stages of Penicillin and Cephalosporin Biosynthesis and ACV Synthetase -- 2.2 Isopenicillin N Synthase (IPNS) -- 2.3 Cephalosporin Biosynthesis -- 2.4 Penicillin Acylases -- 2.5 Cephalosporin Acylases/Acyl transferases and Acetylases -- 2.6 Clavam Biosynthesis -- 2.7 Carbapenem Biosynthesis -- 3 β-Lactamases and Related Enzymes -- 4 Penicillins and Cephalosporins -- 5 Carbacephems -- 6 Penems -- 7 Clavams and Oxacephems -- 8 Trinems and Related Compounds -- 9 Carbapenems -- 10 Azetidinones -- 10.1 Synthesis of Azetidinones -- 10.2 N-Chemistry -- 10.3 C-3, C-3΄ and C-4, C-4́ Chemistry -- 10.4 Other Chemistry -- 10.5 Further Uses of Azetidinones and New Applications -- 11 Related Systems -- 12 Major Structural Variants -- 13 Appendix A: Review Articles -- 14 Appendix B: Additional Articles -- References.