Cleavable surfactants
View Patent ↗The invention provides surfactant compounds of formulas I-IX, which can be used in methods for aiding the solubilization, digestion, preparation, analysis, and/or characterization of biological material, for example, proteins or cell membranes. The compounds can also aid in the recovery of peptides generated during protein digestion, particularly for in-gel digestion protocol. Additionally, the compounds can improve enzymatic protein deglycosylation without interfering with downstream sample preparation steps and mass spectrometric analysis. The compounds can be specifically useful as digestion aids that can be decomposed by an acid, by heat, or a combination thereof. Decomposition of the surfactants allows for facile separation from isolated samples, and/or allows for analysis of the sample without interfering with the sensitivity of various analytical techniques.
1. A compound of formula I:
wherein:
Q is (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, (C 5 -C 10 )heteroaryl, or (C 6 -C 10 )aryl-NH(C 1 -C 6 )alkyl;
Y is —O—C(═Z)—X—;
Z is O or S;
A is aryl, aryl(C 1 -C 6 )alkyl, heteroaryl, or a direct bond;
X is O, NH, or S;
V is C;
M is H, an alkali metal, or tetra(C 1 -C 20 )alkylammonium;
L is —X—C(═Z)—X— or a direct bond;
R 1 is (C 6 -C 16 )aryl, or (C 5 -C 10 )heteroaryl;
R 2 and R 3 are each independently H or (C 10 -C 12 )alkyl;
wherein any alkyl, alkenyl, aryl, or heteroaryl, carbocyclic ring, or heterocyclic ring, is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) (C 1 -C 20 )alkyl, (C 2 -C 20 )alkenyl, (C 2 -C 10 )alkynyl, (C 3 -C 10 )cycloalkyl, (C 1 -C 20 )alkoxy, (C 1 -C 20 )alkylcarbonyl, (C 1 -C 20 )alkylcarboxyl, halo, hydroxyl, —CO 2 R x , —SO 2 R x , —SO 3 R x , nitro, amino, N(R x ) 2 , mercapto, (C 1 -C 20 )alkylthio, (C 6 -C 16 )aryl, (C 6 -C 30 )arylthio, trifluoromethyl, ═O, heteroaryl, or heterocycle groups; provided that Q is not substituted with CO 2 H; and
each R x is independently H, (C 1 C 6 )alkyl, (C 6 -C 16 )aryl, or (C 1 C 6 )alkyl-(C 6 -C 16 )aryl; or a salt thereof; and
wherein R 2 and R 3 are not both H.
2. The compound of claim 1 wherein Q is (C 1 -C 6 )alkyl, phenyl, or phenyl-NH(C 1 -C 6 )alkyl.
3. The compound of claim 1 wherein A is a direct bond.
4. The compound of claim 1 wherein V is C and L is a direct bond.
5. The compound of claim 1 wherein the compound is
a salt thereof.
6. A composition comprising a gel and a compound of claim 1 .
7. The compound of claim 1 , wherein said (C 10 -C 12 )alkyl is a straight-chain C 10 -alkyl or a straight-chain C 12 -alkyl.