- Structure-delivery relationships of lysine-based gemini surfactants and their lipoplexes
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The synthesis and properties of gemini surfactants of the type (R 1(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R1 = C8, C10, C12, C14, C16, and C18) and, for R1 = C18, the degree of unsaturation. For R1(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared. The potential of the gemini surfactants to transfer polynucleotides across a cell membrane was investigated by transfection of HeLa cells with beta-galactosidase, both in the presence and absence of the helper lipid DOPE. Oleoyl was found to be by far the best hydrophobic tail for this biological activity, whereas the effect of the lysine stereochemistry was less pronounced. The effect of an optimum spacer length (n = 6) was observed only in the absence of helper lipid. The most active surfactant, i.e. the one with oleoyl chains and n = 6, formed liposomes with sizes in the range of 60-350 nm, and its lipoplex underwent a transition from a lamellar to a hexagonal morphology upon lowering the pH from 7 to 3. the Partner Organisations 2014.
- Damen, Mark,Cristobal-Lecina, Edgar,Sanmarti, Gloria Colom,Van Dongen, Stijn F.M.,Garcia Rodriguez, Cristina L.,Dolbnya, Igor P.,Nolte, Roeland J.M.,Feiters, Martin C.
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Read Online
- Syntheses of Enantiopure 1,2-Ethylenediamines with Tethered Secondary Amines of the Formula H 2NCH 2CH[(CH 2) nNHMe]NH 2(n = 1-4) from α-Amino Acids: New Agents for Asymmetric Catalysis
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Tris(hydrochloride) adducts of the title compounds-are prepared from the inexpensive α-amino acids H 2 N(C=O)CH 2 CH(NH 2)CO 2 H, HO(C=O)(CH 2) n ′ CH(NH 2)CO 2 H (n ′ = 1, 2), and H2 N(CH 2) 4 CH(NH 2)CO 2 H, respectively (steps/overall yield = 5/32, 7/30, 7/33, 5/38). The NH 2 group that is remote from the secondary amine is installed via BH 3 reduction of an amide [-(C=O)NR 2[ derived?-from an α-amino carboxylic acid. The MeNHCH 2 units are introduced by BH 3 reductions of alkyl carbamate [RO(C=O)NHCH 2-; R = Et, t-Bu] or amide [MeHN(C=O)-] moieties.
- Kabes, Connor Q.,Gunn, Jack H.,Selbst, Maximilian A.,Lucas, Reagan F.,Gladysz, John A.
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p. 3277 - 3285
(2020/11/02)
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- Serine- and threonine-derived diamine equivalents for site-specific incorporation of platinum centers in peptides, and the anticancer potential of these conjugates
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A modular strategy that allows introduction of one or more reactive platinum units at chosen locations along a peptide sequence is presented. This makes use of diazides generated from serine and threonine as diamine equivalents which can be conjugated to the peptide under standard coupling conditions. Reduction of these diazides using Pd/C and H2 followed by platination affords the final products in good yields. Following this, we prepared a new class of peptide-platinum conjugates and carried out preliminary cytotoxicity evaluation and DNA interaction studies. Inclusion of lysine residues in the sequence was found to improve DNA interaction and anticancer activities compared to analogous conjugates with hydrophobic side chains.
- Kumbhakonam, Sateeshkumar,Vellaisamy, Kasipandi,Saroj, Soumya,Venkatesan, Nalini,Karunagaran,Manheri, Muraleedharan Kannoth
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supporting information
p. 2450 - 2458
(2018/02/19)
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- CHIRAL CYCLEN COMPOUNDS AND THEIR USES
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The present invention relates to the preparation of a series of chiral DOTA, D03A, D02A, DO1A, cyclen and their metal complexes, which display properties superior to those of previous DOTA- based compounds, and hence are potentially valuable as a platform for diagnostic applications. The chiral DOTAs reveal a high abundance of twisted square antiprism (TSA) geometry favoring them to be used as potential MRI contrast agents, whereas their rapid labelling properties at mild conditions make them excellent candidates for use as radiometal chelators.
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Paragraph 0088; 0174
(2018/04/13)
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- Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity
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A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC50 values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.
- Satyanarayana, Mavurapu,Kim, Young-Ah,Rzuczek, Suzanne G.,Pilch, Daniel S.,Liu, Angela A.,Liu, Leroy F.,Rice, Joseph E.,LaVoie, Edmond J.
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scheme or table
p. 3150 - 3154
(2010/09/10)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula I: wherein A, B, D, E, R1, R2, R3, R4, R5, X, and ----- have any values defined herein, as well as salts thereof. The compounds have activity as G-quadruplex DNA stabilizers and as anti-proliferative agents.
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Page/Page column 25
(2009/07/03)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula (I) wherein A, B, R1, F, G, n, n' and the dotted line have any values defined herein, as well as salts thereof. The compounds have activity as anti-proliferative agents.
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Page/Page column 49
(2009/03/07)
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- PROCESS FOR THE PREPARATION OF ε-ALKOXYCARBONYLLYSINES AND THEIR ANALOGUES
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A process for the preparation of ω-alkoxycarbonylamino-α-aminoacids and α,ω orthogonally diprotected diaminoacids from α,ω-diaminoacids using 1- alkoxycarbonylbenzotriazoles as protecting agents is disclosed. In an alternative embodiment, carbamoylating agents in the presence of benzotriazoles are used instead of 1-alkoxycarbonylbenzotriazoles. This reaction is preferably applied to the preparation of ε- alkoxycarbonyllysines from lysine. A process for the preparation of t-butoxycarbonylbenzotriazoles and novel complexes of ω-alkoxycarbonylamino-α-aminoacids with benzotriazoles are also disclosed.
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Page/Page column 17-18
(2008/06/13)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula I: wherein A, B, D, E, R1, R2, R3, R4, R5, X, and ----- have any values defined herein, as well as salts thereof. The compounds have activity as G-quadruplex DNA stabalizers and as anti-proliferative agents.
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Page/Page column 34
(2008/06/13)
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- Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors
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A series of novel transglutaminase inhibitors was prepared, based on the scaffold of a commonly used peptide substrate and bearing an electrophilic maleimide group. These compounds were evaluated in vitro and shown to lead to irreversible inactivation of tissue transglutaminase. Comparison with inhibitors studied previously provides insight into the steric environment of the enzyme active site.
- Halim, Dany,Caron, Karine,Keillor, Jeffrey W.
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p. 305 - 308
(2007/10/03)
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- A large scale synthesis of mono- and di-urethane derivatives of lysine
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In the search for a practical route to lysine diurethane derivatives useful for peptide synthesis, we elaborated the synthesis of N(ε)-tert- butoxycarbonyl-L-lysine copper(II) complex (1). This served as substrate for obtaining N(ε)-tert-butoxycarbonyl-L-lysine (2), N(α)-benzyloxycarbonyl- N(ε)-tert-butoxycarbonyl-L-lysine dicyclohexylamine salt (3) and N(α)-(9- fluorenyl)methoxycarbonyl-N(ε)-tert-butoxycarbonyl-L-lysine (4).
- Wiejak, Stanislaw,Masiukiewicz, Elzbieta,Rzeszotarska, Barbara
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p. 1489 - 1490
(2007/10/03)
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- Synthesis of hexapeptide and tetrapeptide analogues of the immunomodulating peptides
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Two hexapeptide and two tetrapeptide analogues of the bioactive hexapeptides [(Trp/Met/Phe)-Lys-Tyr-(Met/Val)-(Pro/Val)-Met] have been synthesized by incorporating novel peptide isosteres such as 2-isoxazoline, (E)-alkene, and reduced amide isosteres. These immunomodulating hexapeptides are known to stimulate the formation of inositol phosphates in lymphocyte cell lines.
- Lee, Ju Young,Chung, Yong Jun,Bae, Yoe-Sik,Ryu, Sung Ho,Kim, Byeang Hyean
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p. 359 - 365
(2007/10/03)
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- 3,5-substituted 4,5-dihydroisoxazoles as transglutaminase inhibitors
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The present invention is directed to certain 3,5 substituted, 4,5-dihydroisoxazoles, and methods for their use. These compounds are transgulatminase inhibitors, and are particularly effective in the inhibition of epidermal transglutaminase and the treatment of acne.
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- AMINO THIOL DIPEPTIDES
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Amino thiol substituted dipeptides of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.
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- Polypeptides, processes for their production, pharmaceutical compositions comprising said polypeptides and their use
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Straight-chain and mono-cyclic polypeptides containing the basic sequence STR1 wherein X is an amino acid residue, the residues in the 1- and 6-positions being linked by an --S--S-- bridge when the polypeptide is monocyclic, have pharmacological, in particular GH--, gastric- and pancreatic-secretion inhibiting activity.
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- Mild and Simple Biomimetic Conversion of Amines to Carbonyl Compounds
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4-Formyl-1-methylpyridinium benzenesulfonate is a convenient reagent for the chemical modification of primary amines to aldehydes and ketones.This method mimics the biological process for transamination reactions with pyridoxal (vitamin b6).As in that process, it involves imine formation, prototropic rearrangement, and hydrolysis.The conditions are extremely mild and are compatible with a large variety of sensitive functional groups.This process provides a simple and a efficient alternative to the somewhat harsher procedures generally employed for such transformations.
- Buckley, Thomas F.,Rapoport, Henry
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p. 4446 - 4450
(2007/10/02)
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