Self-association behavior of an amphiphilic drug nortriptyline hydrochloride under the influence of inorganic salts

AbstractDysfunction of YEATS-domain-containing MLLT1, an acetyl/acyl-lysine dependent epigenetic reader domain, has been implicated in the development of aggressive cancers. Mutations in the YEATS domain have been recently reported as a cause of MLLT1 aberrant reader function. However, structural basis for the reported alterations in affinity for acetyled/acylated histone has remained elusive. Here, we report the crystal structures of both insertion and substitution present in cancer, revealing significant conformational changes of the YEATS-domain loop 8. Structural comparison demonstrates that such alteration not only altered the binding interface for acetylated/acylated histones, but the sequence alterations in the T1 loop may enable dimeric assembly consistent inducing self-association behavior. Nevertheless, we show that also the MLLT1 mutants can be targeted by developed acetyllysine mimetic inhibitors with affinities similarly to wild type. Our report provides a structural basis for the altered behaviors and potential strategy for targeting oncogenic MLLT1 mutants.

Download Full-text

A New Associative Diblock Copolymer of Poly(ethylene glycol) and Dense 1,2,3‐Triazole Blocks: Self‐Association Behavior and Thermoresponsiveness in Water

Macromolecular Chemistry and Physics ◽

10.1002/macp.201900317 ◽

2019 ◽

Vol 220 (21) ◽

pp. 1900317 ◽

Cited By ~ 3

Author(s):

Yanqiong Yang ◽

Akihito Hashidzume

Keyword(s):

Ethylene Glycol ◽

Diblock Copolymer ◽

Poly Ethylene Glycol ◽

Association Behavior ◽

Self Association ◽

Poly Ethylene

Download Full-text

Salt Effect on the Cloud Point Phenomenon of Amphiphilic Drug-Hydroxypropylmethyl Cellulose System

Journal of Chemistry ◽

10.1155/2014/293972 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Mohd. Sajid Ali ◽

Dileep Kumar ◽

Hamad A. Al-Lohedan

Keyword(s):

Cloud Point ◽

Sodium Salt ◽

Salt Effect ◽

Tricyclic Antidepressant ◽

High Concentration ◽

Hydroxypropylmethyl Cellulose ◽

Amphiphilic Drug ◽

Amphiphilic Drugs ◽

Nortriptyline Hydrochloride

Effect of two amphiphilic drugs (tricyclic antidepressant, nortriptyline hydrochloride (NORT), and nonsteroidal anti-inflammatory drug, sodium salt of ibuprofen (IBF)) on the cloud point of biopolymer hydroxypropylmethyl cellulose (HPMC) was studied. Effect of NaCl was also seen on the CP of HPMC-drug system. CP of HPMC increases uniformly on increasing the (drug). Both drugs, though one being anionic (IBF) and other cationic (NORT), affect the CP in almost the same manner but with different extent implying the role of hydrophobicity in the interaction between drug and polymer. Salt affects the CP of the drug in a dramatic way as low concentration of salt was only able to increase the value of the CP, though not affecting the pattern. However, in presence of high concentration of salts, minimum was observed on CP versus (drug) plots. Various thermodynamic parameters were evaluated and discussed on the basis of the observed results.

Download Full-text

Native-like structure and self-association behavior of apolipoprotein A-I in a water/n-propanol solution

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(94)90202-x ◽

1994 ◽

Vol 1212 (3) ◽

pp. 285-294 ◽

Cited By ~ 26

Author(s):

Arnaud Leroy ◽

Ana Jonas

Keyword(s):

Apolipoprotein A ◽

Association Behavior ◽

Self Association ◽

Propanol Solution

Download Full-text

Self-association of copolymers with various composition profiles

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc2009539 ◽

2010 ◽

Vol 75 (4) ◽

pp. 493-505 ◽

Cited By ~ 8

Author(s):

Jitka Kuldová ◽

Peter Košovan ◽

Zuzana Limpouchová ◽

Karel Procházka ◽

Oleg V. Borisov

Keyword(s):

Self Assembly ◽

Diblock Copolymers ◽

Monte Carlo Study ◽

Pair Interaction ◽

Selective Solvents ◽

Structure Of Associates ◽

Association Behavior ◽

Composition Profiles ◽

Self Association

In this paper, we present Monte Carlo study of the self-assembly of linear copolymers consisting of two types of segments (well soluble A and insoluble B segments) in selective solvents. We used simple lattice model: chains were represented by self-avoiding random walks and quality of solvent for both types of segments was controlled by pair interaction parameters. We analyzed how the association behavior depends on the composition profile, i.e., on the sequence of segments A and B along the chain. The size and structure of associates formed by chains with different composition profiles were compared with those of diblock copolymers with the same content of A and B segments. It was shown that even small changes in the sequence of segments within the chains lead to significant differences in the association behavior. In addition to composition profiles, we also shown how the association behavior depends on the quality of solvent and copolymer concentration.

Download Full-text