The author of 《Fatty acid conjugation enhances potency of antisense oligonucleotides in muscle》 were Prakash, Thazha P.; Mullick, Adam E.; Lee, Richard G.; Yu, Jinghua; Yeh, Steve T.; Low, Audrey; Chappell, Alfred E.; Oestergaard, Michael E.; Murray, Sue; Gaus, Hans J.; Swayze, Eric E.; Seth, Punit P.. And the article was published in Nucleic Acids Research in 2019. Formula: C6H15NO The author mentioned the following in the article:
Enhancing the functional uptake of antisense oligonucleotide (ASO) in the muscle will be beneficial for developing ASO therapeutics targeting genes expressed in the muscle. We hypothesized that improving albumin binding will facilitate traversal of ASO from the blood compartment to the interstitium of the muscle tissues to enhance ASO functional uptake. We synthesized structurally diverse saturated and unsaturated fatty acid conjugated ASOs with a range of hydrophobicity. The binding affinity of ASO fatty acid conjugates to plasma proteins improved with fatty acid chain length and highest binding affinity was observed with ASO conjugates containing fatty acid chain length from 16 to 22 carbons. The degree of unsaturation or conformation of double bond appears to have no influence on protein binding or activity of ASO fatty acid conjugates. Activity of fatty acid ASO conjugates correlated with the affinity to albumin and the tightest albumin binder exhibited the highest activity improvement in muscle. Palmitic acid conjugation increases ASO plasma Cmax and improved delivery of ASO to interstitial space of mouse muscle. Conjugation of palmitic acid improved potency of DMPK, Cav3, CD36 and Malat-1 ASOs (3- to 7-fold) in mouse muscle. Our approach provides a foundation for developing more effective therapeutic ASOs for muscle disorders. After reading the article, we found that the author used 6-Aminohexan-1-ol(cas: 4048-33-3Formula: C6H15NO)
6-Aminohexan-1-ol(cas: 4048-33-3) may be used along with glutaric acid to generate poly(ester amide)s with excellent film- and fiber forming properties. It can undergo cyclization over copper supported on γ-alumina and magnesia to form hexahydro-1H-azepine.Formula: C6H15NO
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