579
Views
0
CrossRef citations to date
0
Altmetric
Review

Synthesis of Chemically Modified Bioactive Peptides: Recent Advances, Challenges and Developments for Medicinal Chemistry

, &
Pages 1289-1310 | Published online: 21 Oct 2009

Bibliography

  • Lipinski CA , LombardoF, DominyBW, FeeneyPJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.Adv. Drug Deliv. Rev.46, 3–26 (2001).
  • Marx V . Watching peptide drugs grow up.Chem. Eng. News83, 17–24 (2005).
  • Houben-Weyl Methods of Organic Chemistry (Vol. E22) Synthesis of Peptides and Peptidomimetics . GoodmanM (Ed.). Georg Thieme Verlag, Stuttgart, Germany (2003).
  • Sewald N , JakubkeHD. Peptides: Chemistry and Biology. Wiley-VCH, Weinheim, Germany (2009).
  • Kates SA , SolNA, Albericio,F, BaranyG. Peptides: Design, Synthesis and Biological Activity. BasavaC, AnantharamaiahGM (Eds). Birkhäuser, Boston, MA, USA (1994).
  • Kessler H . Conformation and biological activity of cyclic peptides.Angew. Chem. Int. Ed.21, 512–523 (1982).
  • Werle M , Bernkop-SchnürchA. Strategies to improve plasma half life time of peptide and protein drugs.Amino Acids30, 351–367 (2006).
  • Lien S , LowmanHB. Therapeutic peptides.Trends Biotechnol.21, 556–562 (2003).
  • Hayden C . GnRH analogues: applications in assisted reproductive techniques.Eur. J. Endocrinol.159(Suppl. 1), S17–S25 (2008).
  • Scott CL , HolmbergT. Castration of sex offenders: prisoners’ rights versus public safety.J. Am. Acad. Psychiatry Law31, 502–509 (2003).
  • Weckbecker G , LewisI, AlbertR, SchmidHA, HoyerD, BrunsC. Opportunities in somatostatin research: biological, chemical and therapeutic aspects.Nat. Rev. Drug Disc.2, 999–1017 (2003).
  • Vallette S , SerriO. Octreotide LAR for the treatment of acromegaly.Expert Opin. Drug Metab. Toxicol.4, 783–793 (2008).
  • Lyndrup J , LamontRF. The choice of a tocolytic for the treatment of preterm labor: a critical evaluation of nifedipine versus atosiban.Expert Opin. Investig. Drugs16, 843–853 (2007).
  • Vande Walle J , StocknerM, RaesA, N⊘rgaardJP. Desmopressin 30 years in clinical use: a safety review.Curr. Drug Saf.2, 232–238 (2007).
  • Epstein TG , BernsteinJA. Current and emerging management options for hereditary angioedema in the US.Drugs68, 2561–2573 (2008).
  • Edelman S , MaierH, WilhelmK. Pramlintide in the treatment of diabetes mellitus.BioDrugs22, 375–386 (2008).
  • Nielsen LL , YoungAA, ParkesDG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of Type 2 diabetes.Regul. Pept.117, 77–88 (2004).
  • Lettino M , ToschiV. Direct antithrombins: new perspectives in cardiovascular medicine.Curr. Med. Chem. Cardiovasc. Hematol. Agents.2, 267–275 (2004).
  • Warkentin TE , KosterA. Bivalirudin: a review.Expert Opin. Pharmacother.6, 1349–1371 (2005).
  • Billich A . Thymosin α1. SciClone Pharmaceuticals.Curr. Opin. Investig. Drugs3, 698–707 (2002).
  • Mandava P , ThiagarajanP, KentTA. Glycoprotein IIb/IIIa antagonists in acute ischaemic stroke: current status and future directions.Drugs68, 1019–1028 (2008).
  • Xia Z , ChenY, ZhuY, WangF, XuX, ZhanJ. Recombinant ω-conotoxin MVIIA possesses strong analgesic activity.BioDrugs20, 275–281 (2006).
  • Dechantsreiter MA , PlankerE, MathäBet al. N-methylated cyclic RGD peptides as highly active and selective αVβ3 integrin antagonists. J. Med. Chem.42, 3033–3040 (1999).
  • Burke P , DeNardoS, MiersL, LambornK, MatzkuS, DeNardoG. Cilengitide targeting of αVβ3 integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res.62, 4263–4272 (2002).
  • Goodman SL , HölzemannG, SulyokGA, KesslerH. Nanomolar small molecule inhibitors for αVβ6, αVβ5, and αVβ3 integrins. J. Med. Chem.45, 1045–1051 (2002).
  • Reardon DA , NaborsLB, StuppR, MikkelsenT. Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme.Expert Opin. Investig. Drugs17, 1225–1235 (2008).
  • Masuoka Y , ShindohN, InamuraN. Histone deacetylase inhibitors from microorganisms: the Astellas experience.Prog. Drug Res.66, 337–359 (2008).
  • Janin YL . Peptides with anticancer use or potential.Amino Acids25, 1–40 (2003).
  • Gilon C , MangC, LohofE, FriedlerA, KesslerH. Synthesis of cyclic peptides. In: Houben-Weyl, Methods of Organic Chemistry (Vol. E22) Synthesis of Peptides and Peptidomimetics. Goodman M (Ed.), Georg Thieme Verlag, Stuttgart, Germany (2003).
  • Davies JS . The cyclization of peptides and depsipeptides.J. Pept. Sci.9, 471–501 (2003).
  • Montalbetti CAGN , FalqueV. Amide bond formation and peptide coupling.Tetrahedron61, 10827–10852 (2005).
  • Valeur E , BradleyM. Amide bond formation: beyond the myth of coupling reagents.Chem. Soc. Rev.38, 606–631 (2009).
  • Meutermans WDF , GoldingSW, BourneGTet al. Synthesis of difficult cyclic peptides by inclusion of a novel photolabile auxiliary in a ring contraction strategy. J. Am. Chem. Soc. 121, 9790–9796 (1999).
  • Miranda LP , MeutermansWDF, SmytheML, AlewoodPF. An activated O-N acyl transfer auxiliary: efficient amide-backbone substitution of hindered ‘difficult’ peptides. J. Org. Chem.65, 5460–5468 (2000).
  • Horton DA , BourneGT, CoughlanJet al. Cyclic tetrapeptides via the ring contraction strategy: chemical techniques useful for their identification. Org. Biomol. Chem. 6, 1386–1395 (2008).
  • Meutermans WDF , BourneGT, GoldingSWet al. Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides. Org. Lett. 5, 2711–2714 (2003).
  • Shao Y , LuW, KentSBH. A novel method to synthesize cyclic peptides.Tetrahedron Lett.39, 3911–3914 (1998).
  • Taniguchi A , SkwarczynskiM, SohmaYet al. Controlled production of amyloid b peptide from a photo-triggered, water-soluble precursor ‘click peptide’. ChemBioChem 9, 3055–3065 (2008).
  • Coin I , BeyermannM, BienertM. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences.Nat. Protoc.2, 3247–3256 (2007).
  • Skwarczynski M , KisoY. Application of the O-N intramolecular acyl migration reaction in medicinal chemistry. Curr. Med. Chem.14, 2813–2823 (2007).
  • Tuchscherer G , ChandravarkarA, CamusMSet al. Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis. Biopolymers 88, 239–252 (2007).
  • Lécaillon J , GillesP, SubraG, MartinezJ, AmblardM. Synthesis of cyclic peptides via O-N-acyl migration. Tetrahedron Lett.49, 4674–4676 (2008).
  • Miller SJ , BlackwellHE, GrubbsRH. Application of ring-closing metathesis to the synthesis of rigidified amino acids and peptides.J. Am. Chem. Soc.118, 9606 (1996).
  • Stymiest JL , MitchellBF, WongS, VederasJC. Synthesis of biologically active dicarba analogues of the peptide hormone oxytocin using ring-closing metathesis.Org. Lett.5, 47–49 (2003).
  • Stymiest JL , MitchellBF, WongS, VederasJC. Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability.J. Org. Chem.70, 7799–7809 (2005).
  • Berezowska I , ChungNN, LemieuxC, WilkesBC, SchillerPW. Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH2 retain high opioid activity. J. Med. Chem.50, 1414–1417 (2007).
  • Mollica A , GuardianiG, DavisPet al. Synthesis of stable and potent δ/µ opioid peptides: analogues of H-Tyr-c[D-Cys-Gly-PheD-Cys]-OH by ring-closing metathesis. J. Med. Chem. 50, 3138–3142 (2007).
  • Miles SM , LeatherbarrowRJ, MarsdenSP, CoatsWJ. Synthesis and bio-assay of RCM-derived Bowman-Birk inhibitor analogues.Org. Biomol. Chem.2, 281–283 (2005).
  • Robinson AJ , ElaridiJ, Van Lierop BJ, Mujcinovic S, Jackson E. Microwave-assisted RCM for the synthesis of carbocyclic peptides. J. Pept. Sci.13, 280–285 (2007).
  • Pattabiraman VR , StymiestJL, DerksenDJ, MartinNI, VederasJC. Multiple on-resin olefin metathesis to form ring-expanded analogues of the lantibiotic peptide, lacticin 3147 A2.Org. Lett.9, 699–702 (2007).
  • Ghalit N , ReichweinJF, HilbersHW, BreukinkE, RijkersDTS, LiskampRMJ. Synthesis of bicyclic alkene-/alkane-bridged nisin mimics by ring-closing metathesis and their biochemical evaluation as lipid II binders: toward the design of potential novel antibiotics.ChemBioChem18, 1540–1554 (2007).
  • Ghalit N , KemminkJ, HilbersHW, VersluisC, RijkersDTS, LiskampRMJ. Step-wise and pre-organization induced synthesis of a crossed alkene-bridged nisin Z DE-ring mimic by ring-closing metathesis.Org. Biomol. Chem.5, 924–934 (2007).
  • Hruby VJ . Designing peptide receptor agonists and antagonists.Nat. Rev. Drug Discov.1, 847–858 (2002).
  • Schmiedeberg N , KesslerH. Reversible backbone protection enables combinatorial solid-phase ring-closing metathesis reaction (RCM) in peptides.Org. Lett.4, 59–62 (2001).
  • Brik A . Metathesis in peptides and peptidomimetics.Adv. Synth. Catal.350, 1661–1675 (2008).
  • Dekker FJ , de Mol NJ, Fischer MJE, Kemmink J, Liskamp RMJ. Role of solution conformation and flexibility of short peptide ligands that bind to the p56(lck) SH2 domain. Org. Biomol. Chem.1, 3297–3303 (2003).
  • Wang D , LiuM, AroraPS. Inhibition of HIV-1 fusion by hydrogen-bond-surrogate-based α helices.Angew. Chem. Int. Ed.47, 1879–1882 (2008).
  • Boyle TP , BremnerJB, CoatesJet al. New cyclic peptides via ring-closing metathesis reactions and their anti-bacterial activities. Tetrahedron 64, 11270–11290 (2008).
  • Hossain MA , RosengrenKJ, ZhangSet al. Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity. Org. Biomol. Chem. 7, 1547–1553 (2009).
  • Harris PWR , BrimbleMA. Synthesis of macrocyclic analogues of the neuroprotective agent glycyl-l-prolyl-l-glutamic acid (GPE).Org. Biomol. Chem.4, 2696–2709 (2006).
  • Lawrence J , JourdanM, ValléeY, BlandinV. Peptide cyclization via ring-closing metathesis: the N-alkenoxy peptide approach. Org. Biomol. Chem.6, 4575–4581 (2008).
  • Illesinghe J , GuoCX, GarlandRet al. Metathesis assisted synthesis of cyclic peptides. Chem. Commun. 3, 295–297 (2009).
  • Angell YL , BurgessK. Peptidomimetics via copper-catalyzed azide–alkyne cycloadditions.Chem. Soc. Rev.36, 1674–1689 (2007).
  • Roice M , JohannsenI, MeldalM. High capacity poly(ethylene glycol) based amino polymers for peptide and organic synthesis.QSAR Comb. Sci.23, 662–673 (2004).
  • Cantel S , Le Chevalier IsaadA, ScrimaMet al. Synthesis and conformational analysis of a cyclic peptide obtained via i to i+4 intramolecular sidechain to sidechain azide-alkyne 1,3-dipolar cycloaddition. J. Org. Chem.73, 5663–5674 (2008).
  • Le Chevalier Isaad A , PapiniAM, ChorevM, RoveroP. Side chain-to-side-chain cyclization by click reaction.J. Pept. Sci.15, 451–454 (2009).
  • Bock VD , SpeijerD, HiemstraH, van Maarseveen JH. 1,2,3-triazoles as peptide bond isosteres: synthesis and biological evaluation of cyclotetrapeptide mimics. Org. Biomol. Chem.5, 971–975 (2007).
  • Liu Y , ZhangL, WanJ, LiY, XuY, PanY. Design and synthesis of cyclo[-Arg-Gly-Asp-ψ(triazole)-Gly-Xaa-] peptide analogues by click chemistry.Tetrahedron64, 10728–10734 (2008).
  • Punna S , KuzelkaJ, WangQ, FinnMG. Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition.Angew. Chem. Int. Ed.44, 2215–2220 (2005).
  • van Maarseveen JH , HorneWS, GhadiriMR. Efficient route to C-2 symmetric heterocyclic backbone modified cyclic peptides.Org. Lett.7, 4503–4506 (2005).
  • Angell Y , BurgessK. Ring closure to β-turn mimics via copper-catalyzed azide/alkyne cycloadditions.J. Org. Chem.70, 9595–9598 (2005).
  • Goncalves V , GautierB, RegazzettiAet al. On-resin cyclization of peptide ligands of the vascular endothelial growth factor receptor 1 by copper(I)-catalyzed 1,3-dipolar azide–alkyne cycloaddition. Bioorg. Med. Chem. Lett. 17, 5590–5594 (2007).
  • Turner RA , OliverAG, LokeyRS. Click chemistry as a macrocyclization tool in the solid-phase synthesis of small cyclic peptides.Org. Lett.9, 5011–5014 (2007).
  • Bock VD , PerciaccanteR, JansenTP, HiemstraH, van Maarseveen JH. Click chemistry as a route to cyclic tetrapeptide analogues: synthesis of cyclo-[Pro-Val-ψ(triazole)-Pro-Tyr]. Org. Lett.8, 919–922 (2006).
  • Himo F , LovellT, HilgrafRet al. Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. J. Am. Chem. Soc. 127, 210–216 (2005).
  • Horne WS , OlsenCA, BeierleHM, MonteroA, GhadiriMR. Probing the bioactive conformation of an archetypal natural product HDAC inhibitor with conformationally homogeneous triazole-modified cyclic tetrapeptides.Angew. Chem. Int. Ed.48, 4718–4724 (2009).
  • Beierle JM , HorneWS, van Maarseveen JH, Waser B, Reubi JC, Ghadiri MR. Conformationally heterogeneous heterocyclic pseudotetrapeptides as three-dimensional scaffolds for rational drug design: receptor-selective somatostatin analogues. Angew. Chem. Int. Ed.48, 4725–4729 (2009).
  • Köhn M , BreinbauerR. The Staudinger ligation – a gift to chemical biology.Angew. Chem. Int. Ed.43, 3106–3116 (2004).
  • Nilsson BL , KiesslingLL, RainesRT. Staudinger ligation: a peptide from a thioester and azide.Org. Lett.2, 1939–1941 (2000).
  • Saxon E , ArmstrongJI, BertozziCR. A ‘traceless’ Staudinger ligation for the chemoselective synthesis of amide bonds.Org. Lett.2, 2141–2143 (2000).
  • Soellner MB , TamA, RainesRT. Staudinger ligation of peptides at non-glycyl residues.J. Org. Chem.71, 9824–9830 (2006).
  • Soellner MB , NilssonBL, RainesRT. Reaction mechanism and kinetics of the traceless Staudinger ligation.J. Am. Chem. Soc.128, 8820–8828 (2006).
  • Liu L , Hong Z-Y, Wong C-H. Convergent glycopeptide synthesis by traceless Staudinger ligation and enzymatic coupling. ChemBioChem7, 429–432 (2006).
  • Tam A , SoellnerMB, RainesRT. Water-soluble phosphinothiols for traceless Staudinger ligation and integration with expressed protein ligation.J. Am. Chem. Soc.129, 11421–11430 (2007).
  • Tam A , SoellnerMB, RainesRT. Electronic and steric effects on the rate of the traceless Staudinger ligation.Org. Biomol. Chem.6, 1173–1175 (2008).
  • David O , MeesterWJN, BieräugelH, HiemstraH, van Maarseveen JH. Intramolecular Staudinger ligation: a powerful ring-closure method to form medium-sized lactams. Angew. Chem. Int. Ed.42, 4373- 4375 (2003).
  • Masson G , den Hartog T, Schoemaker HE, Hiemstra H, van Maarseveen JH. Intramolecular Staudinger ligation towards biaryl-containing lactams. Synlett6, 865–868 (2006).
  • Kleineweischede R , HackenbergerCPR. Chemoselective peptide cyclization by traceless Staudinger ligation.Angew. Chem. Int. Ed.47, 5984–5988 (2008).
  • Friedler A , FriedlerD, LuedtkeNWet al. Development of a functional backbone cyclic mimetic of the HIV-1 Tat arginine-rich motif. J. Biol. Chem. 275, 23783–23789 (2000).
  • Hess S , OvadiaO, ShalevDEet al. Effect of structural and conformation modifications, including backbone cyclization, of hydrophilic hexapeptides on their intestinal permeability and enzymatic stability. J. Med. Chem. 50, 6201–6211 (2007).
  • Gazal S , GellermanG, ZivOet al. Human somatostatin receptor specificity of backbone-cyclic analogues containing novel sulfur building units. J. Med. Chem. 45, 1665–1671 (2002).
  • Zeltser I , Ben-AzizO, ScheflerIet al. Insect neuropeptide antagonist. Part II. Synthesis and biological activity of backbone cyclic and precyclic PBAN antagonists. J. Pept. Res. 58, 275–284 (2001).
  • Gilon C , ZeltserI, DanielSet al. Rationally designed neuropeptide antagonists: a novel approach for generation of environmentally friendly insecticides. Invertebr. Neurosci. 3, 245–250 (1997).
  • Qvit N , ReuveniH, GazalSet al. Synthesis of a novel macrocyclic library: discovery of an IGF-1R inhibitor. J. Comb. Chem. 10, 256–266 (2008).
  • Weide T , ModlingerA, KesslerH. Spatial screening for the identification of the bioactive conformation of integrin ligands.Top. Curr. Chem.272, 1–50 (2007).
  • Haubner R , FinsingerD, KesslerH. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the αVβ3 integrin for a new cancer therapy. Angew. Chem. Int. Ed.36, 1374–1389 (1997).
  • Boer J , GottschlingD, SchusterAet al. Design and synthesis of potent and selective α4β7 integrin antagonists. J. Med. Chem. 44, 2586–2592 (2001).
  • Tucker GC . Integrins: molecular targets in cancer therapy.Curr. Oncol. Rep.8, 96–103 (2006).
  • Bächle D , LoersG, GuthöhrleinEW, SchachnerM, SewaldN. Glycomimetic cyclopeptides stimulate neurite outgrowth.Angew. Chem. Int. Ed.45, 6582–6585 (2006).
  • Simova O , IrintchevA, MehannaAet al. Carbohydrate mimics promote functional recovery after peripheral nerve repair. Ann. Neurol. 60, 430–437 (2006).
  • Aguilar MI , PurcellAW, DeviRet al. β-Amino acid-containing hybrid peptides – new opportunities in peptidomimetics. Org. Biomol. Chem. 5, 2884–2890 (2007).
  • Joshi RM , ChauhanCH. Synthesis of peptides based on α,β-didehydro α-amino acids. In: Houben-Weyl, Methods of Organic Chemistry (Vol. E22) Synthesis of Peptides and Peptidomimetics. GoodmanM (Ed.). Georg Thieme Verlag, Stuttgart, Germany (2003).
  • Mathur P , RamakumarS, ChauhanVS. Peptide design using α,β-dehydro amino acids: from β-turns to helical hairpins. Biopolymers (Pept. Sci.)76, 150–161 (2004).
  • Toniolo C , CrismaM, FormaggioF, PeggionC. Control of peptide conformation by the Thorpe-Ingold effect (C-α-tetrasubstitution).Biopolymers (Pept. Sci.)60, 396–419 (2001).
  • Wu YD , HanW, WangDP, GaoY, ZhaoYL. Theoretical analysis of secondary structures of β-peptides.Acc. Chem. Res.41, 1418–1427 (2008).
  • Chatterjee S , RoyRS, BalaramSR. Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acids.J. R. Soc. Interface4, 587–606 (2007).
  • Schumann F , MüllerA, KokschM, MüllerG, SewaldN. Are β-amino acids γ-turn mimetics? Exploring a new design principle for bioactive cyclopeptides.J. Am. Chem. Soc.122, 12009–12010 (2000).
  • Maleševic M , MajerZ, VassEet al. Spectroscopic detection of pseudo-turns in homodetic cyclic penta- and hexapeptides comprising β-homoproline. Int. J. Pept. Res. Ther. 12, 165–177 (2006).
  • Urman S , GausK, YangYet al. The constrained amino acid β-Acc confers potency and selectivity to integrin ligands. Angew. Chem. Int. Ed. Engl. 46, 3976–3978 (2007).
  • Hamada Y , ShioiriT. Recent progress of the synthetic studies of biologically active marine cyclic peptides and depsipeptides.Chem. Rev.105, 4441–4482 (2005).
  • Harris KS , CaseyJL, ColeyAMet al. Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning. J. Biol. Chem. 284, 9361–9371 (2009).
  • Teixidó M , ZuritaE, MalakoutikhahM, TarragóT, GiraltE. Diketopiperazines as a tool for the study of transport across the blood–brain barrier (BBB) and their potential use as BBB-shuttles.J. Am. Chem. Soc.129, 11802–11813 (2007).
  • Bergseng E , XiaJ, KimCY, KhoslaC, SollidLM. Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the Celiac disease-associated HLA-DQ2 molecule.J. Biol. Chem.280, 21791–21796 (2005).
  • Conradi R , HilgersA, HoN, BurtonP. The influence of peptide structure on transport across Caco-2 cells. II. Peptide-bond modification which results in improved permeability.Pharm. Res.9, 435–439 (1992).
  • Sagan S , KaroyanP, LequinO, Chassaing,G, LavielleS. N- and Cα-methylation in biologically active peptides: synthesis, structural and functional aspects Curr. Med. Chem.11, 2799–2822 (2004).
  • Linde Y , OvadiaO, SafraiEet al. Structure-activity relationship and metabolic stability studies of backbone cyclization and N-methylation of melanocortin peptides. Biopolymers 90, 671–682 (2008).
  • Rajeswaran WG , HocartSJ, MurphyWA, TaylorJE, CoyDH. N-methyl scan of somatostatin octapeptide agonists produces interesting effects on receptor subtype specificity. J. Med. Chem.44, 1416–1421 (2001).
  • Rajeswaran WG , HocartSJ, MurphyWA, TaylorJE, CoyDH. Highly potent and subtype selective ligands derived by N-methyl scan of a somatostatin antagonists. J. Med. Chem.44, 1305–1311 (2001).
  • Chatterjee J , OvadiaO, ZahnGet al. Multiple N-methylation by a designed approach enhances receptor selectivity. J. Med. Chem. 50, 5878–5881 (2007).
  • Biron E , ChatterjeeJ, OvadiaOet al. Improving oral bioavailability of peptides by multiple N-methylation: somatostatin analogs. Angew. Chem. Int. Ed. 47, 2595–2599 (2008).
  • Teixidó M , AlbericioF, GiraltE. Solid-phase synthesis and characterization of N-methyl-rich peptides. J. Peptide Res.65, 153–166 (2005).
  • Sewald N . Efficient, racemization-free peptide coupling of N-alkyl amino acids by using amino acid chlorides generated in situ – total syntheses of the cyclopeptides cyclosporin O and omphalotin A. Angew. Chem. Int. Ed.41, 4661–4663 (2002).
  • Biron E , KesslerH. Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase peptide synthesis. J. Org. Chem.70, 5183–5189 (2005).
  • Biron E , ChatterjeeJ, KesslerH. Optimized selective N-methylation of peptides on solid support. J. Pept. Sci.12, 213–219 (2006).
  • Demmer O , DijkgraafI, SchotteliusM, WesterHJ, KesslerH. Introduction of functional groups into peptides via N-alkylation. Org. Lett.10, 2015–2018 (2008).
  • Chatterjee J , MierkeD, KesslerH. N-methylated cyclic pentaalanine peptides as template structures. J. Am. Chem. Soc.128, 15164–15172 (2006).
  • Chatterjee J , MierkeDF, KesslerH. Conformational preference and potential templates of N-methylated cyclic pentaalanine peptides. Chem. Eur. J.14, 1508–1517 (2008).
  • Chatterjee J , GilonC, HoffmanA, KesslerH. N-methylation of peptides: a new perspective in medicinal chemistry. Acc. Chem. Res.41, 1331–1342 (2008).
  • Tulla-Puche J , MarcucciE, Prats-AlfonsoE, Bayó-PuxanN, AlbericioF. NMe amide as a synthetic surrogate for the thioester moiety in thiocoraline. J. Med. Chem.52, 834–839 (2009).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.