SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF BOC- PROTECTED FLUORESCENT ARGININE
Marshall, Sarah Ruth
Small peptides capable of penetrating or spanning the hydrophobic core of lipid bilayers have many potential uses in medicine and in biochemical research. As the most basic of the amino acids that can comprise such peptides, arginine (pKa ~ 13.8) is one of the few naturally-occurring molecules capable of existing in a cationic form even when it is deep within the nonpolar membrane interior. In fact, an unambiguously neutral arginine inside of a membrane has never been reported. To allow for molecular-level tracking of peptide localization, a fluorescent arginine derivative (Boc-Arg*-OH) was prepared from commercially available backbone-protected arginine. Palladium(0)-catalyzed coupling of the side-chain to a 4-bromo-1,8-naphthalimide affords the derivative in yields of about 10%. The presence of the fluorophore lowers the pKa of the side-chain guanidinium group by several orders of magnitude, to 9.0 (± 0.1), allowing the derivative to access an electrically neutral protonation state that is not generally available to arginine itself. Fluorescence emission from the neutral form of Boc-Arg*-OH is red-shifted by ~100 nm relative to that of the positively-charged form, which appears in the 430-475 nm range depending on solvent polarity and H-bonding ability. Emission from the neutral form can be observed even under acidic conditions, suggesting that intermolecular excited state deprotonation, an uncommonly seen transfer of hydrogen ions between the fluorophore and solvent upon excitation, is occurring. Attempts to attach Boc-Arg*-OH at the N-terminal position of peptides like substance P (RPKPQQFFGLM-NH2) using solid-phase peptide synthesis were unsuccessful. This failure is attributed to a competing intramolecular cyclization that occurs when Boc-Arg*-OH is activated by agents like HBTU.
Marshall, Sarah Ruth. (August 2017). SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF BOC- PROTECTED FLUORESCENT ARGININE (Master's Thesis, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/6518.)
Marshall, Sarah Ruth. SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF BOC- PROTECTED FLUORESCENT ARGININE. Master's Thesis. East Carolina University, August 2017. The Scholarship. http://hdl.handle.net/10342/6518. April 21, 2019.
Marshall, Sarah Ruth, “SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF BOC- PROTECTED FLUORESCENT ARGININE” (Master's Thesis., East Carolina University, August 2017).
Marshall, Sarah Ruth. SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF BOC- PROTECTED FLUORESCENT ARGININE [Master's Thesis]. Greenville, NC: East Carolina University; August 2017.
East Carolina University