ʻO nā peptide kahi papa o nā pūhui i hana ʻia e ka hoʻohui ʻana o nā waikawa amino lehulehu ma o nā paʻa peptide.Aia lākou ma nā wahi a pau i nā mea ola.A hiki i kēia manawa, ua loaʻa nā ʻumi tausani o nā peptides i nā mea ola.He kuleana koʻikoʻi ka Peptides i ka hoʻoponopono ʻana i nā hana hana o nā ʻōnaehana like ʻole, nā ʻāpana, nā ʻiʻo a me nā ʻāpana a me nā hana ola, a hoʻohana pinepine ʻia i ka loiloi hana, ka noiʻi antibody, ka hoʻomohala ʻana i ka lāʻau a me nā kula ʻē aʻe.Me ka hoʻomohala ʻana o ka biotechnology a me ka ʻenehana synthesis peptide, ua hoʻomohala a hoʻohana ʻia nā lāʻau peptide hou aʻe i loko o ke keʻena.
Nui nā ʻano hoʻololi peptide, hiki ke hoʻokaʻawale ʻia i ka hoʻololi post a me ka hoʻololi ʻana i ke kaʻina hana (me ka hoʻololi ʻana i ka waikawa amino acid), a me ka hoʻololi ʻana o N-terminal, hoʻololi C-terminal, hoʻololi i ke kaulahao ʻaoʻao, hoʻololi ʻana i ka waikawa amino, hoʻololi iwi iwi, etc., ma muli o ke kahua hoʻololi (Figure 1).Ma ke ʻano he mea nui e hoʻololi i ke ʻano o ke kaulahao nui a i ʻole nā hui kaulahao ʻaoʻao o nā kaulahao peptide, hiki i ka hoʻololi ʻana o ka peptide ke hoʻololi pono i nā waiwai kino a me nā kemika o nā pūhui peptide, hoʻonui i ka solubility wai, hoʻolōʻihi i ka manawa hana i loko o ka vivo, hoʻololi i kā lākou hāʻawi olaola, hoʻopau i ka immunogenicity. , hōʻemi i nā hopena ʻawaʻawa, a pēlā aku. Ma kēia pepa, ua hoʻolauna ʻia kekahi mau hoʻolālā hoʻololi peptide nui a me ko lākou mau ʻano.
1. Ka'ilikala
ʻO nā peptides cyclic he nui nā noi i ka biomedicine, a he nui nā peptides kūlohelohe me ka hana biological he peptides cyclic.No ka mea, ʻoi aku ka paʻakikī o nā peptides cyclic ma mua o nā peptides linear, ua kūpaʻa loa lākou i ka ʻōnaehana digestive, hiki ke ola i loko o ka digestive tract, a hōʻike i kahi pilina ikaika no nā mea loaʻa.ʻO ka Cyclization ke ala pololei loa e synthesize i nā peptides cyclic, ʻoi aku hoʻi no nā peptides me ka iwi nui.E like me ke ʻano o ka cyclization, hiki ke hoʻokaʻawale ʻia i ke ʻano kaulahao ʻaoʻao ʻaoʻao, ke ʻano o ke kaulahao ʻaoʻao, ke ʻano o ke kaulahao ʻaoʻao, ke ʻano o ka hopena.
(1) sidechain-a-sidechain
ʻO ke ʻano maʻamau o ke kaulahao ʻaoʻao i ka ʻaoʻao-chain cyclization ʻo ka disulfide bridging ma waena o nā koena cysteine.Hoʻokomo ʻia kēia cyclization e nā koena cysteine e hoʻoneʻe ʻia a laila hoʻoneʻe ʻia e hana i nā paʻa disulfide.Hiki ke hoʻokō ʻia ka synthesis polycyclic ma ka wehe ʻana i nā pūʻulu pale sulfhydryl.Hiki ke hana ʻia ka Cyclization ma kahi mea hoʻoheheʻe post-dissociation a i ʻole ma kahi resin pre-dissociation.ʻOi aku ka maikaʻi o ka cyclization ma nā resins ma mua o ka solvent cyclization no ka mea ʻaʻole hiki i nā peptides ma nā resins ke hana i nā conformations cyclified.ʻO kekahi ʻano ʻaoʻao ʻaoʻao - ʻaoʻao kaulahao cyclization ʻo ia ka hoʻokumu ʻana i kahi ʻano amide ma waena o kahi aspartic acid a i ʻole glutamic acid koena a me ka base amino acid, e koi ana i ka hui pale kaulahao ʻaoʻao e hiki ke koho ʻia mai ka polypeptide a i ʻole. ma ka resin a ma hope paha o ka wehe ʻana.ʻO ke kolu o ke ʻano o ke kaulahao ʻaoʻao - ʻaoʻao cyclization ka hoʻokumu ʻana i nā diphenyl ethers e tyrosine a i ʻole p-hydroxyphenylglycine.Loaʻa kēia ʻano cyclization i nā huahana kūlohelohe i nā huahana microbial, a loaʻa pinepine nā huahana cyclization i ka waiwai lapaʻau.ʻO ka hoʻomākaukau ʻana i kēia mau pūhui e koi i nā kūlana kūʻokoʻa, no laila ʻaʻole hoʻohana pinepine ʻia i ka synthesis o nā peptides maʻamau.
(2) pahu-a-ʻaoʻao kaulahao
ʻO ka cyclization kaulahao ʻaoʻao terminal ka mea maʻamau i ka C-terminal me ka pūʻulu amino o ke kaulahao ʻaoʻao lysine a ornithine, a i ʻole ka N-terminal me ka aspartic acid a i ʻole ke kaulahao ʻaoʻao glutamic acid.Hana ʻia nā cyclization polypeptide ʻē aʻe ma o ka hoʻokumu ʻana i nā paʻa ether ma waena o ka pahu C a me nā kaulahao ʻaoʻao serine a i ʻole threonine.
(3) Terminal a i ʻole ke ʻano poʻo i ka huelo
Hiki ke kaʻa ʻia nā polypeptides kaulahao i loko o kahi solvent a i hoʻopaʻa ʻia paha ma ka resin ma ka ʻaoʻao kaulahao cyclation.Pono e hoʻohana ʻia nā haʻahaʻa haʻahaʻa o nā peptides i ka solvent centralization e pale aku i ka oligomerization o nā peptides.ʻO ka hua o kahi polypeptide synthetic ring head-to-tail ma muli o ke kaʻina o ka polypeptide kaulahao.No laila, ma mua o ka hoʻomākaukau ʻana i nā peptides cyclic ma ke ʻano nui, pono e hana mua ʻia kahi waihona o nā peptides alakaʻi kaulahao hiki ke hana ʻia, a ma hope o ka cyclization e ʻike i ke kaʻina me nā hopena maikaʻi loa.
2. N-methylation
Hoʻomaka mua ʻia ka N-methylation i nā peptides kūlohelohe a hoʻokomo ʻia i loko o ka peptide synthesis e pale ai i ka hoʻokumu ʻana o nā paʻa hydrogen, a laila e hoʻoikaika i nā peptides i ka biodegradation a me ka hoʻomaʻemaʻe.ʻO ka synthesis o nā peptides me ka hoʻohana ʻana i nā derivatives amino acid N-methylated ke ʻano koʻikoʻi.Eia kekahi, hiki ke hoʻohana ʻia ka hopena Mitsunobu o N-(2-nitrobenzene sulfonyl chloride) polypeptide-resin intermediates me ka methanol.Ua hoʻohana ʻia kēia ʻano hana no ka hoʻomākaukau ʻana i nā hale waihona puke cyclic peptide i loaʻa nā waikawa amino N-methylated.
3. Phosphorylation
ʻO ka Phosphorylation kekahi o nā hoʻololi maʻamau ma hope o ka unuhi ʻana ma ke ʻano.I loko o nā pūnaewele kanaka, ʻoi aku ma mua o 30% o nā protein i phosphorylated.He kuleana koʻikoʻi ka Phosphorylation, ka phosphorylation hiki ke hoʻohuli ʻia, i ka hoʻomalu ʻana i nā kaʻina cellular he nui, e like me ka hoʻololi ʻana i ka hōʻailona, ka hōʻike gene, ka pōʻai cell a me ka hoʻoponopono cytoskeleton, a me ka apoptosis.
Hiki ke ʻike ʻia ka Phosphorylation ma nā koena waikawa amino like ʻole, akā ʻo nā mea nui o ka phosphorylation maʻamau he serine, threonine, a me nā koena tyrosine.Hiki ke hoʻokomo ʻia nā derivatives phosphotyrosine, phosphothreonine, a me phosphoserine i nā peptides i ka wā synthesis a i hana ʻia ma hope o ka synthesis peptide.Hiki ke hoʻokō ʻia ka phosphorylation koho me ka hoʻohana ʻana i ke koena o ka serine, threonine, a me tyrosine e wehe i nā pūʻulu pale.Hiki i kekahi mau phosphorylation reagents ke hoʻokomo i nā pūʻulu waikawa phosphoric i loko o ka polypeptide ma o ka hoʻololi ʻana.I nā makahiki i hala iho nei, ua hoʻokō ʻia ka phosphorylation kikoʻī o ka lysine me ka hoʻohana ʻana i ka hopena Staudinger-phosphite koho (Figure 3).
4. Myristoylation a me palmitoylation
ʻO ka Acylation o ka N-terminal me nā momona momona e hiki ai i nā peptides a i ʻole nā protein ke hoʻopaʻa i nā membrane cell.ʻO ka myridamoylated sequence ma ka N-terminal hiki iā Src family protein kinases a hoʻohuli i ka transcriptase Gaq proteins e kuhikuhi ʻia e hoʻopaʻa i nā membrane cell.Ua hoʻopili ʻia ka myristic acid i ka N-terminal o ka resin-polypeptide me ka hoʻohana ʻana i nā hopena hoʻohui maʻamau, a hiki ke hoʻokaʻawale ʻia ka hopena lipopeptide ma lalo o nā kūlana maʻamau a hoʻomaʻemaʻe ʻia e RP-HPLC.
5. Glycosylation
ʻO nā Glycopeptides e like me vancomycin a me teicolanin he mau lāʻau antibiotic koʻikoʻi no ka mālama ʻana i nā maʻi bacterial kūʻē i ka lāʻau, a hoʻohana pinepine ʻia nā glycopeptides e hoʻoulu i ka ʻōnaehana pale.Eia kekahi, no ka mea he nui nā microbial antigens i glycosylated, he mea nui ia e aʻo i nā glycopeptides no ka hoʻomaikaʻi ʻana i ka hopena therapeutic o ka maʻi.Ma ka ʻaoʻao ʻē aʻe, ua ʻike ʻia ʻo nā protein ma ka membrane cell o nā cell tumor e hōʻike ana i ka glycosylation abnormal, ka mea e hana nui ai nā glycopeptides i ka maʻi kanesa a me ka noiʻi pale pale pale.Hoʻomākaukau ʻia nā Glycopeptides e ke ʻano Fmoc/t-Bu.Hoʻokomo pinepine ʻia nā koena glycosylated, e like me ka threonine a me ka serine, i loko o nā polypeptides e ka pentafluorophenol ester i hoʻāla ʻia i nā fMOC e pale i nā waikawa amino glycosylated.
6. Isoprene
Hana ʻia ka isopentadienylation ma nā koena cysteine ma ka ʻaoʻao kaulahao kokoke i ka C-terminal.Hiki i ka protein isoprene ke hoʻomaikaʻi i ka pili o ka membrane cell a hana i ka pilina protein-protein.ʻO nā protein isopentadienated ka tyrosine phosphatase, GTase liʻiliʻi, nā molekole cochaperone, lamina nuklea, a me nā protein paʻa centromeric.Hiki ke hoʻomākaukau ʻia nā polypeptides isoprene me ka hoʻohana ʻana i ka isoprene ma ka resins a i ʻole ma ka hoʻokomo ʻana i nā derivatives cysteine.
7. Hoʻololi polyethylene glycol (PEG).
Hiki ke hoʻohana ʻia ka hoʻololi PEG e hoʻomaikaʻi i ke kūpaʻa hydrolytic protein, biodistribution a me ka peptide solubility.ʻO ka hoʻokomo ʻana i nā kaulahao PEG i nā peptides hiki ke hoʻomaikaʻi i kā lākou mau waiwai pharmacological a ke kāohi pū i ka hydrolysis o nā peptides e nā enzymes proteolytic.ʻOi aku ka maʻalahi o nā peptides PEG ma ka ʻāpana glomerular capillary cross ma mua o nā peptides maʻamau, e hōʻemi nui ana i ka hoʻomaʻemaʻe renal.Ma muli o ka lōʻihi o ka hapalua ola o nā peptides PEG i loko o ka vivo, hiki ke mālama ʻia ka pae lapaʻau maʻamau me nā haʻahaʻa haʻahaʻa a me nā lāʻau peptide liʻiliʻi pinepine.Eia nō naʻe, he hopena maikaʻi ʻole ka hoʻololi ʻana o PEG.ʻO ka nui o ka PEG e pale aku i ka enzyme mai ka hoʻohaʻahaʻa ʻana i ka peptide a e hōʻemi hoʻi i ka hoʻopaʻa ʻana o ka peptide i ka mea i loaʻa.Akā ʻo ka haʻahaʻa haʻahaʻa o ka PEG peptides e hoʻopau pinepine ʻia e ko lākou pharmacokinetic half-life lōʻihi, a ma ka noho lōʻihi ʻana i ke kino, ʻoi aku ka nui o nā peptides PEG e komo i loko o nā ʻiʻo.No laila, pono e hoʻonui ʻia nā kikoʻī polymer PEG no nā hopena maikaʻi loa.Ma ka ʻaoʻao ʻē aʻe, hōʻiliʻili ʻia nā peptides PEG i loko o ke ake ma muli o ka emi ʻana o ka renal clearance, ka hopena o ka macromolecular syndrome.No laila, pono e hoʻolālā maikaʻi ʻia nā hoʻololi PEG ke hoʻohana ʻia nā peptides no ka hoʻāʻo ʻana i ka lāʻau.
Hiki ke hōʻuluʻulu ʻia nā hui hoʻololi maʻamau o nā mea hoʻololi PEG penei: Amino (-amine) -NH2, aminomethyl-Ch2-NH2, hydroxy-OH, carboxy-Cooh, sulfhydryl (-Thiol) -SH, Maleimide -MAL, succinimide carbonate - SC, succinimide acetate -SCM, succinimide propionate -SPA, n-hydroxysuccinimide -NHS, Acrylate-ch2ch2cooh, aldehyde -CHO (e like me propional-ald, butyrALD), kumu acrylic (-acrylate-acrl), azido-azide, biotinyl - ʻO Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, etc. Hiki ke hoʻohui ʻia nā derivatives PEG me nā waikawa carboxylic i n-terminal amines a i ʻole nā kaulahao ʻaoʻao lysine.Hiki ke hoʻohui ʻia ka PEG i hoʻohana ʻia ʻo Amino me ka aspartic acid a i ʻole nā kaulahao ʻaoʻao glutamic acid.Hiki ke hoʻohui ʻia ʻo PEG mal-activated i ka mercaptan o nā kaulahao ʻaoʻao cysteine i hoʻopau piha ʻia [11].Hoʻokaʻawale ʻia nā mea hoʻololi PEG penei (nota: ʻo ka mPEG methoxy-PEG, CH3O-(CH2CH2O)n-CH2CH2-OH):
(1) mea hoʻololi PEG kaulahao pololei
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) hoʻololi PEG bifunctional
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl·NH2-PEG-COOH, MAL-PEG-NHS
(3) lālā hoʻololi PEG
(mPEG)2-NHS, (mPEG)2-ALD, (mPEG)2-NH2, (mPEG)2-MAL
8. ʻO ka biotinization
Hiki ke hoʻopaʻa ikaika ʻia ka biotin me avidin a i ʻole streptavidin, a ʻo ka ikaika hoʻopaʻa ʻana ua kokoke loa i ka covalent bond.Hoʻohana mau ʻia nā peptides i hōʻailona ʻia i ka biotin i ka immunoassay, histocytochemistry, a me ka fluorescence-based flow cytometry.Hiki ke hoʻohana ʻia nā antibodies antibiotin i kapa ʻia e hoʻopaʻa i nā peptides biotinylated.Hoʻopili pinepine ʻia nā lepili biotin i ke kaulahao ʻaoʻao lysine a i ʻole ka pahu N.Hoʻohana pinepine ʻia ka 6-aminocaproic acid i mea paʻa ma waena o nā peptides a me biotin.Hiki ke maʻalahi ka paʻa i ka hoʻopaʻa ʻana i ka substrate a hoʻopaʻa maikaʻi i ke alo o ka steric hindrance.
9. ʻO ka hōʻailona ʻana i ka fluorescent
Hiki ke hoʻohana ʻia ka lepili fluorescent e ʻimi i nā polypeptides i loko o nā cell ola a e aʻo i nā enzyme a me nā hana o ka hana.ʻO Tryptophan (Trp) he fluorescent, no laila hiki ke hoʻohana ʻia no ka hōʻailona intrinsic.ʻO ka spectrum emission o tryptophan e pili ana i ke kaiapuni peripheral a emi iho me ka emi ʻana o ka solvent polarity, kahi waiwai e pono ai no ka ʻike ʻana i ke ʻano peptide a me ka hoʻopaʻa ʻana i ka mea hoʻopaʻa.Hiki ke hoʻopau ʻia ka fluorescence tryptophan e ka protonated aspartic acid a me ka glutamic acid, hiki ke kaupalena i kona hoʻohana ʻana.ʻO ka Dansyl chloride pūʻulu (Dansyl) he mea ʻoluʻolu loa ke hoʻopaʻa ʻia i kahi hui amino a hoʻohana pinepine ʻia ma ke ʻano he lepili fluorescent no nā waikawa amino a i ʻole nā protein.
Hiki ke hoʻololi i ka ikehu (FRET) no nā haʻawina enzyme.Ke hoʻohana ʻia ʻo FRET, ʻo ka polypeptide substrate ka mea maʻamau i loaʻa i kahi pūʻulu hōʻailona fluorescence a me kahi pūʻulu fluorescence-quenching.Hoʻopiʻi ʻia nā pūʻulu fluorescent i hōʻailona ʻia e ka mea kinai ma o ka hoʻoili ʻana i ka ikehu photon.Ke hoʻokaʻawale ʻia ka peptide mai ka enzyme i nīnau ʻia, hoʻopuka ka pūʻulu lepili i ka fluorescence.
10. Cage polypeptides
Loaʻa i nā peptides Cage nā pūʻulu pale e pale i ka peptide mai ka hoʻopaʻa ʻana i ka mea loaʻa.Ke ʻike ʻia i ka radiation UV, hoʻāla ʻia ka peptide, e hoʻihoʻi i kona pili i ka mea loaʻa.No ka mea hiki ke hoʻomalu ʻia kēia hoʻoulu ʻana e like me ka manawa, amplitude, a i ʻole wahi, hiki ke hoʻohana ʻia nā peptides cage e aʻo i nā hopena e kū nei i loko o nā cell.ʻO nā pūʻulu pale i hoʻohana pinepine ʻia no ka polypeptides cage he mau pūʻulu 2-nitrobenzyl a me kā lākou derivatives, hiki ke hoʻokomo ʻia i ka peptide synthesis ma o nā derivatives amino acid derivatives.ʻO nā derivatives amino acid i kūkulu ʻia he lysine, cysteine, serine, a me tyrosine.ʻAʻole hoʻohana maʻamau ʻia nā derivatives Aspartate a me ka glutamate ma muli o ko lākou maʻalahi i ka cyclization i ka wā o ka peptide synthesis a me ka dissociation.
11. Polyantigenic peptide (MAP)
ʻAʻole pale ʻia nā peptides pōkole a pono e hui pū ʻia me nā protein lawe e hana i nā antibodies.Hoʻokumu ʻia ka peptide polyantigenic (MAP) i nā peptides like ʻole i hoʻopili ʻia me ka lysine nuclei, hiki ke hōʻike kikoʻī i nā immunogens kiʻekiʻe a hiki ke hoʻohana ʻia e hoʻomākaukau i nā hui pūmua peptide-carrier.Hiki ke hoʻopili ʻia nā polypeptides MAP e ka hoʻohui ʻana i ka pae paʻa ma ka resin MAP.Eia nō naʻe, ʻo ka hoʻohui ʻole ʻana e hopena i nā kaulahao peptide i ʻoki ʻia ma kekahi mau lālā a no laila ʻaʻole hōʻike i nā waiwai o ka polypeptide MAP kumu.Ma ke ʻano he ʻokoʻa, hiki ke hoʻomākaukau a hoʻomaʻemaʻe ʻia nā peptides a laila hui pū ʻia me MAP.ʻO ke kaʻina peptide i hoʻopili ʻia i ka peptide core ua wehewehe maikaʻi ʻia a ʻike maʻalahi ʻia e ka spectrometry mass.
Ka hopena
ʻO ka hoʻololi ʻana i ka peptide kahi ala nui o ka hoʻolālā ʻana i nā peptides.ʻAʻole hiki i nā peptides hoʻololi kemika ke mālama i ka hana biological kiʻekiʻe, akā e pale maikaʻi hoʻi i nā drawbacks o ka immunogenicity a me ka toxicity.I ka manawa like, hiki i ka hoʻololi kemika ke hāʻawi i nā peptides me kekahi mau waiwai maikaʻi hou.I nā makahiki i hala iho nei, ua hoʻomohala wikiwiki ʻia ke ʻano o ka hoʻoulu ʻana o CH no ka hoʻololi ʻana i nā polypeptides, a ua loaʻa nā hopena koʻikoʻi.
Ka manawa hoʻouna: Mar-20-2023