Synlett, Inhaltsverzeichnis Synlett DOI: 10.1055/a-2536-8969 letter Small Molecules in Medicinal Chemistry Design and Synthesis of a C 2-Symmetric Cyclic Decapeptide and Its Peptidomimetic as Potential Inhibitors against Amyloid-β Aggregation Takuya Kobayakawa‡ , Kenichi Yamamoto‡ , Aiichiro Fukutome , Marisa Arioka , Kohei Tsuji , Hirokazu Tamamura ∗ Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract A C 2-symmetric cyclic decapeptide and its peptidomimetic based on the KLVFF fragment of amyloid-β (Aβ) are designed and synthesized as potential inhibitors against Aβ aggregation in Alzheimer’s disease. These compounds are efficiently synthesized using solution- and solid-phase peptide synthesis. Thioflavin-T assays reveal that both the cyclic decapeptide and its chloroalkene dipeptide isostere (CADI)-containing peptidomimetic significantly inhibit Aβ aggregation. These results demonstrate the potential of C 2-symmetric cyclic peptides and peptidomimetics as effective Aβ aggregation inhibitors for Alzheimer’s disease therapies. Key words Key wordscyclic decapeptide - peptidomimetic - C 2-symmetric - peptide synthesis - Alzheimer’s disease Volltext Referenzen References 1 Holtzman DM, Morris JC, Goate AM. Sci. Transl. Med. 2011; 3: 77sr1 2 Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Alzheimers Demen. 2007; 3: 186 3 Hardy J, Selkoe DJ. Science 2002; 297: 353 4 Selkoe DJ. Behav. Brain Res. 2008; 192: 106 5 Chimon S, Shaibat MA, Jones CR, Calero DC, Aizezi B, Ishii Y. Nat. Struct. Mol. Biol. 2007; 14: 1157 6 Tjernberg LO, Näslund J, Lindqvist F, Johansson J, Karlström AR, Thyberg J, Terenius L, Nordstedt C. J. Biol. Chem. 1996; 271: 8545 7a Soto C, Sigurdsson EM, Morelli L, Asok Kumar R, Castaño EM. Nat. Med. 1998; 4: 822 7b Arai T, Araya T, Sasaki D, Taniguchi A, Sato T, Sohma Y, Kanai M. Angew. Chem. Int. Ed. 2014; 53: 8236 7c Etienne MA, Aucoin JP, Fu Y, McCarley RL, Hammer RP. J. Am. Chem. Soc. 2006; 128: 3522 8 Chalifour RJ, McLaughlin RW, Lavoie L, Morissette C, Tremblay N, Boule M, Sarazin P, Stea D, Lacombe D, Tremblay P, Gervais F. J. Biol. Chem. 2003; 278: 34874 9 Gordon DJ, Sciarretta KL, Meredith SC. Biochemistry 2001; 40: 8237 10 Hamman JH, Enslin GM, Kotzé AF. BioDrugs 2005; 19: 165 11 White CJ, Yudin AK. Nat. Chem. 2011; 3: 509 12 Giordanetto F, Kihlberg J. J. Med. Chem. 2014; 57: 278 13 Robertson M, Bremner JB, Coates J, Deadman J, Keller PA, Pyne SG, Somphol K, Rhodes DI. Eur. J. Med. Chem. 2011; 46: 4201 14 Alexander LD, Sellers RP, Davis MR, Ardi VC, Johnson VA, Vasko RC, McAlpine SR. J. Med. Chem. 2009; 52: 7927 15 Basak A, Mitra D, Das AK, Mohottalage D, Basak A. Bioorg. Med. Chem. Lett. 2010; 20: 3977 16 Kobayakawa T, Narumi T, Tamamura H. Org. Lett. 2015; 17: 2302 17 Kobayakawa T, Tamamura H. Tetrahedron 2016; 72: 4968 18 Kobayakawa T, Tamamura H. Tetrahedron 2017; 73: 4464 19 Kobayakawa T, Matsuzaki Y, Hozumi K, Nomura W, Nomizu M, Tamamura H. ACS Med. Chem. Lett. 2018; 9: 6 20 Kobayakawa T, Azuma C, Watanabe Y, Sawamura S, Taniguchi A, Hayashi Y, Tsuji K, Tamamura H. J. Org. Chem. 2021; 86: 5091 21 Kobayakawa T, Tsuji K, Tamamura H. Bioorg. Med. Chem. 2024; 110: 117811 22 Barlos K, Gatos D. Pept. Sci. 1999; 51: 266 23 Robak MT, Herbage MA, Ellman JA. Chem. Rev. 2010; 110: 3600 24 Mita T, Higuchi Y, Sato Y. Chem. Eur. J. 2013; 19: 1123 25 LeVine H. Methods Enzymol. 1999; 309: 274 26 Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. J. Neurochem. 2003; 87: 172 Zusatzmaterial Zusatzmaterial Supporting Information
