ʻO ka lāʻau lapaʻau

ʻO ka sodium Inclisiran

ʻO Inclisiran sodium API (Active Pharmaceutical Ingredient) ke aʻo nui ʻia ma ke kahua o ka RNA interference (RNAi) a me nā therapeutics cardiovascular. Ma ke ʻano he siRNA pālua ʻelua e kuhikuhi ana i ka ʻano PCSK9, hoʻohana ʻia ia i ka noiʻi preclinical a me ka noiʻi lapaʻau e loiloi i nā hoʻolālā hoʻopaʻa ʻana i nā gene-silencing lōʻihi no ka hoʻohaʻahaʻa ʻana i ka LDL-C (low-density lipoprotein cholesterol). He mea hoʻohālike ia no ka noiʻi ʻana i nā ʻōnaehana lawe siRNA, kūpaʻa, a me nā therapeutics RNA i hoʻopaʻa ʻia i ka ate.

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Fmoc-Gly-Gly-OH

ʻO Fmoc-Gly-Gly-OH kahi dipeptide i hoʻohana ʻia ma ke ʻano he papa kūkulu hale ma ka solid-phase peptide synthesis (SPPS). Loaʻa iā ia nā koena glycine ʻelua a me kahi Fmoc-protected N-terminus, e ʻae ana i ka elongation chain peptide controlled. Ma muli o ka liʻiliʻi a me ka maʻalahi o ka glycine, ua aʻo pinepine ʻia kēia dipeptide i ka pōʻaiapili o ka peptide backbone dynamics, linker design, a me ka hoʻohālikelike ʻana i nā peptides a me nā protein.

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Fmoc-Thr(tBu)-Phe-OH

ʻO Fmoc-Thr(tBu)-Phe-OH kahi poloka hale dipeptide i hoʻohana mau ʻia i loko o ka solid-phase peptide synthesis (SPPS). Mālama ka pūʻulu Fmoc (9-fluorenylmethyloxycarbonyl) i ka N-terminus, aʻo ka hui tBu (tert-butyl) e pale i ke kaulahao ʻaoʻao hydroxyl o threonine. Hoʻopaʻa ʻia kēia dipeptide pale no kāna kuleana i ka hoʻomaʻamaʻa ʻana i ka elongation peptide kūpono, e hōʻemi ana i ka racemization, a me ka hoʻohālikelike ʻana i nā kumu kikoʻī kikoʻī i ka hoʻolālā protein a me nā haʻawina pili.

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AEEA-AEEA

ʻO AEEA-AEEA he hydrophilic, maʻalahi spacer i hoʻohana mau ʻia i ka peptide a me ka noiʻi conjugation lāʻau. Aia i loko o ʻelua mau ʻāpana ethylene glycol, pono ia no ke aʻo ʻana i nā hopena o ka lōʻihi o ka loulou a me ka maʻalahi i ka pilina molekala, solubility, a me ka hana olaola. Hoʻohana pinepine ka poʻe noiʻi i nā ʻāpana AEEA e loiloi i ka hopena o nā spacers i ka hana o nā antibody-drug conjugates (ADCs), peptide-drug conjugates, a me nā bioconjugates ʻē aʻe.

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Fmoc-L-Lys[Eic(OtBu)-γ-Glu(OtBu)-AEEA]-OH

ʻO kēia pūhui he lysine derivative i hoʻohana ʻia i ka peptide synthesis a me ka hoʻomohala ʻana i ka lāʻau conjugate. Hōʻike ia i kahi pūʻulu Fmoc no ka pale N-terminal, a me kahi hoʻololi ʻaoʻao-chain me Eic(OtBu) (eicosanoic acid derivative), γ-glutamic acid (γ-Glu), a me AEEA (aminoethoxyethoxyacetate). Hoʻolālā ʻia kēia mau ʻāpana e aʻo i nā hopena lipidation, spacer chemistry, a me ka hoʻokuʻu ʻana i ka lāʻau. Ua noiʻi nui ʻia ma ka pōʻaiapili o nā hoʻolālā prodrug, nā mea hoʻopili ADC, a me nā peptides pili membrane.

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Fmoc-L-Lys[Ste(OtBu)-γ-Glu-(OtBu)-AEEA-AEEA]-OH

ʻO kēia pūhui he lysine derivative i hoʻololi ʻia i hoʻohana ʻia i ka peptide synthesis, ʻoi loa no ke kūkulu ʻana i nā conjugates peptide i manaʻo ʻia a multifunctional. Hiki i ka pūʻulu Fmoc ke hana stepwise ma o Fmoc solid-phase peptide synthesis (SPPS). Hoʻololi ʻia ke kaulahao ʻaoʻao me ka stearic acid derivative (Ste), γ-glutamic acid (γ-Glu), a me ʻelua AEEA (aminoethoxyethoxyacetate) linkers, e hāʻawi ana i ka hydrophobicity, nā waiwai uku, a me ka spacing maʻalahi. Hoʻomaʻamaʻa maʻamau ia no kāna kuleana i nā ʻōnaehana hoʻopuka lāʻau, me ka antibody-drug conjugates (ADCs) a me nā peptides e komo ana i ke kelepona.

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Boc-His(Trt)-Aib-Gln(Trt)-Gly-OH

Boc-His(Trt)-Aib-Gln(Trt)-Gly-OHhe tetrapeptide i pale ʻia i hoʻohana ʻia i ka synthesis peptide a me nā haʻawina hoʻolālā. Mālama ka pūʻulu Boc (tert-butyloxycarbonyl) i ka N-terminus, aʻo nā hui Trt (trityl) e pale i nā kaulahao ʻaoʻao o ka histidine a me ka glutamine e pale i nā hopena makemake ʻole. ʻO ka heleʻana o Aib (α-aminoisobutyric acid) e hoʻoikaika i nā conformations helical a hoʻonui i ka paʻa o ka peptide. He waiwai kēia peptide no ka noiʻi ʻana i ka hoʻopili ʻana i ka peptide, kūpaʻa, a ma ke ʻano he scaffold no ka hoʻolālā ʻana i nā peptides hana biologically.

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Boc-Tyr(tBu)-Aib-Glu(OtBu)-Gly-OH

Boc-Tyr(tBu)-Aib-Glu(OtBu)-Gly-OHhe tetrapeptide i pale ʻia i hoʻohana mau ʻia i ka noiʻi synthesis peptide. ʻO nā pūʻulu Boc (tert-butyloxycarbonyl) a me tBu (tert-butyl) he mau pūʻulu pale no ka pale ʻana i nā ʻaoʻao i ka wā o ka hui kaulahao peptide. ʻO ka hoʻokomoʻana o Aib (α-aminoisobutyric acid) e kōkua i ka hoʻouluʻana i nā hanana helical a hoʻonui i ka paʻa o ka peptide. Hoʻopaʻa ʻia kēia kaʻina peptide no kona hiki ke nānā i ka conformational analysis, peptide folding, a ma ke ʻano he hale kūkulu i ka hoʻomohala ʻana i nā peptides bioactive me ka hoʻonui ʻia a me ka kikoʻī.

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Fmoc-Ile-Aib-OH

ʻO Fmoc-Ile-Aib-OH kahi poloka hale dipeptide i hoʻohana ʻia i ka solid-phase peptide synthesis (SPPS). Hoʻohui ia i ka isoleucine pale ʻia Fmoc me Aib (α-aminoisobutyric acid), kahi amino acid non-natural e hoʻonui ai i ka paʻa helix a me ka pale protease.

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Fmoc-L-Lys[Eic(OtBu)-γ-Glu(OtBu)-AEEA-AEEA]-OH

ʻO Fmoc-L-Lys[Eic(OtBu)-γ-Glu(OtBu)-AEEA-AEEA]-OH he mea hoʻohana ʻia ka amino acid building block i hoʻolālā ʻia no ka hāʻawi ʻana i ka lāʻau lapaʻau a me ka bioconjugation. Hōʻike ia i kahi moiety Eic (eicosanoid) no ka pilina lipid, γ-Glu no ka huli ʻana, a me nā spacers AEEA no ka maʻalahi.

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Boc-Tyr(tBu)-Aib-OH

ʻO Boc-Tyr(tBu)-Aib-OH kahi poloka dipeptide pale i hoʻohana ʻia i ka peptide synthesis, e hui pū ana i ka tyrosine pale ʻia ʻo Boc a me Aib (α-aminoisobutyric acid). Hoʻonui ke koena Aib i ka hoʻokumu ʻana i ka helix a me ke kū'ē protease.

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Boc-His(Trt)-Ala-Glu(OtBu)-Gly-OH

ʻO Boc-His(Trt)-Ala-Glu(OtBu)-Gly-OH kahi ʻāpana tetrapeptide i pale ʻia i hoʻohana ʻia i ka solid-phase peptide synthesis (SPPS) a me ka hoʻomohala lāʻau peptide. Loaʻa iā ia nā pūʻulu pale no ka synthesis orthogonal a loaʻa i kahi kaʻina e pono ai i ka hoʻolālā peptide bioactive a me ka structural.

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