Chemical Tools for Studying Directed Cell Migration

Abstract

Cell migration is required for many physiological processes, including wound repair and embroyogenesis, and relies on precisely orchestrated events that are regulated in a spatially and temporally controlled manner. Most traditional approaches for studying migration, such as genetic methods or the use of chemical inhibitors, do not offer insight into these important components of protein function. However, chemical tools, which respond on a more rapid timescale and in localized regions of the cell, are capable of providing more detailed, real-time information. This review describes these recent approaches to investigate cell migration and focuses on proteins that are activated by light or small molecules, as well as fluorescent sensors of protein activity.

Synthesis of Migrastatin Analogues as Inhibitors of Tumour Cell Migration: Exploring Structural Change in and on the Macrocyclic Ring

“…[α]D -20 o (c 1.5, CHCl3); 1 H NMR (CDCl3, 500MHz) δ 5.54 -5.47 (m, 1H, H-8), 5.39 (td, 1H, J7,8 = 10.6, J6,7 = 5.3 Hz, H-7), 4.47 (dd, 1H, J12,12' = 11.5, J12,11 = 3.4 Hz, H-12), 3.82 (dd,1H,J11,12' = 4.5 Hz,3.54 (ddd,1H,J10,11=7.6,J10,OH = 4.9,J9,10 = 2.2 Hz,2.73 (dqd,1H,J8,9 = 9.2,J9,Me = 6.8 Hz,2.42 (ddd,1H,J = 12.9,8.8,4. [α]D 6.49 o (c 0.99, CHCl3); 1 H NMR (CDCl3, 500MHz) δ 5.44 (ddd, 1H, J7,8 = 14.6, J7,6 = 8.0, J7,6' = 6.4 Hz, H-7), 5.28 (dd,1H,J8,9 = 8.1 Hz,4.41 (dd,1H,J12,12' = 10.7,2.8 Hz, 2H,ArH),2H,ArH),7H,ArH),2H,ArH),5.94 (appt,1H,J2',3' =J3',4' = 9.6 Hz, H-3'), 5.69 (dd,1H,J3',4' = J4',5' = 9.7 Hz,3H,10),…”

“…Tumour metastasis is a process where cancer cells detach from a primary tumour, migrate and then colonize a distant organ and the process leads to mortality for cancer patients. [1] Small molecules that interfere with tumour cell migration [2] have significant potential as anti-metastatic drugs [3] or as tools [4] for the study of tumour cell migration. Migrastatin 1, is a natural product that inhibits tumour cell migration (µM range) in vitro.…”

Tightening up the structure, lighting up the pathway: application of molecular constraints and light to manipulate protein folding, self-assembly and function

“…While an in-depth summary [67, 129-132] of the recent advances in this field is beyond the scope of this Review, we would like to highlight several examples to underscore the rapid growth of this exciting research field. For instance, photoremovable protecting groups have been used to trigger acquisition of protein functions [133-135], to investigate enzyme binding and inhibition [136-138], protein translocation [139], chemotactic activity [140], peptide mediated lipid degradation [141], phosphopeptide-binding for signaling pathways [142, 143], and to regulate or control the function or activity of oligonucleotides [144, 145], neurotransmitters [146, 147], hormones [148], and signaling molecules [149, 150].…”

Synthesis of Migrastatin Analogues as Inhibitors of Tumour Cell Migration: Exploring Structural Change in and on the Macrocyclic Ring

“…Tumour metastasis is a process in which cancer cells detach from a primary tumour, migrate and then colonize a distant organ and the process leads to mortality for cancer patients 1. Small molecules that interfere with tumour cell migration2 have significant potential as anti‐metastatic drugs3 or as tools4 for the study of tumour cell migration. Migrastatin ( 1 ), is a natural product that inhibits tumour cell migration (μ M range) in vitro.…”