- Efficient one-pot synthesis of doxorubicin conjugates through its amino group to melanotransferrin p97
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The amino group of doxorubicin 1 is reacted with bis-NHS-ester linkers 6, or anhydrides 13 to offer in high yield modified doxorubicins 7-12 and 14-16, respectively. Compounds 7-12 are mono-NHS-esters, and can be directly coupled with melanotransferrin (p97), a useful vector with the ability to cross the blood-brain barrier, to yield the expected doxorubicin-p97 conjugates. Upon activating the carboxylic group with BTTU, compound 14-16 could be used in the same reaction. Structurally, the amino group of doxorubicin is covalently bonded to the amino groups of p97. The conjugates are potential candidates for treatment of brain tumors.
- Chen, Qingqi,Sowa, Damian A.,Cai, Jianlin,Gabathuler, Reinhard
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Read Online
- Bivalent HIV-1 fusion inhibitors based on peptidomimetics
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Membrane fusion is a valid target for inhibition of HIV-1 replication. A 34-mer fragment peptide (C34), which is contained in the HIV-1 envelope protein gp41, has significant anti-HIV activity. Previously, a dimeric derivative of C34 linked by a disulfide bridge at its C-terminus was found to have more potent anti-HIV activity than the C34 peptide monomer. To date, several peptidomimetic small inhibitors have been reported, but most have lower potency than peptide derivatives related to C34. In the present study we applied this dimerization concept to these peptidomimetic small inhibitors and designed several bivalent peptidomimetic HIV-1 fusion inhibitors. The importance of the length of linkers crosslinking two peptidomimetic compounds was demonstrated and several potent bivalent inhibitors containing tethered peptidomimetics were produced.
- Kobayakawa, Takuya,Ebihara, Kento,Tsuji, Kohei,Kawada, Takuma,Fujino, Masayuki,Honda, Yuzuna,Ohashi, Nami,Murakami, Tsutomu,Tamamura, Hirokazu
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supporting information
(2020/11/07)
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- Multi-functionalization bis(butanediamide) compounds and preparation and use thereof
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The invention discloses compounds used for separating actinide element extractants and a preparation method thereof. The compounds are bis(butanediamide) compounds having the structure represented by the formula 1. Based on summary of an amide extractant structure and extraction efficiency, a series of tetraamide extractants are designed and synthesized, the specific skeleton of diamide is retained, and in the premise of not increasing steric hindrance, more complex sites (functional groups) are introduced, two molecules of diamide are smartly linked through ethylenediamine and derivatives thereof to form the new tetraamide extractants; because the ethylenediamine and the derivatives thereof have shorter carbon chains, relatively large steric hindrance effect cannot be produced, more functional groups are introduced, the complex sites of the extractants with metal ions are correspondingly increased, the complex ability is increased, and thus the dual action can greatly improve the extraction ability of the extractants on uranium and thorium acyl ions.
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Paragraph 0026; 0027
(2016/11/24)
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- Protein crosslinkers, crosslinking methods and applications thereof
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Some aspects of this disclosure relate to a method for crosslinking a biological fluid comprising combining a biological fluid with a crosslinker to covalently crosslink proteins endogenous to the biological fluid to form a crosslinked gel. Examples of a biological fluid are blood, plasma, or serum.
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Page/Page column 18
(2008/06/13)
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- Compounds for protein stabilization and methods for their use
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The present invention is directed to stabilized polypeptide compositions. Typical embodiments of the present invention provide improved methods and materials for maintaining the stability of insulin polypeptide formulations. In particular, the disclosure provided herein teaches that the aggregation of insulin polypeptides can be inhibited by combining them with a class of compounds having the general formula A1—L1—S—L2—A2, wherein S comprises from one to seven consecutive atoms selected from the group consisting of nitrogen, carbon, and oxygen, wherein at least one of the atoms is a carbon atom; L1 and L2 are linking groups having from two to twelve atoms selected from the group consisting of nitrogen, carbon, oxygen, sulfur, and phosphorus; and A1 and A2 are carboxylic acid groups.
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- IMMOBILIZATION OF ENZYMES INTRODUCING SPACERS. A SYNTHESIS OF CARRIERS WITH SPACERS OF VARIOUS LENGTH
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A synthesis of spacers of various length and type, utilizing α,ω-dicarboxylic acids, α,ω-diaminoalkanes and succinic anhydride, condensation with carbodiimide, or introduction of -NCS functional groups is described.Carriers with a spacer were prepared by a method of binding the already synthesized spacer to the carrier (glass), and alternatively, by a stepwise synthesis of the spacer on the carrier surface.Carriers containing functional groups (37.2-39.3 μmol/g -NCS and 25-41.5 μmol/g -COOH) prepared in this way had total length of the spacer 0.62-3.92 nm.Whereas the length of the spacer is of no substantial importance for the reaction with low-molecular substances (L-valine, L-cysteine and 2-mercaptoethanol), the optimum length of the spacer for high-molecular compounds (albumin) is about 1.75-2.05 nm.The hydroxyl group adjacent to the functional group of the spacer (1,3-diaminopropan-2-ol) is also of noticeable influence.
- Flemming, Christian,Gabert, Anton,Wand, Helmut,Zemek, Jiri
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p. 184 - 191
(2007/10/02)
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