Tyr4 bbn

The DB4 (N₄-Pro-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH₂, N₄ = 6-(carboxy)-1,4,8,11-tetraazaundecane) and SG4 (DOTA-DGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH₂, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) peptide conjugates (Figure 1) were provided by PiChem (Graz, Austria). [Tyr⁴]BBN (Pyr-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂) was purchased from Bachem (Bubendorf, Switzerland). The neprilysin (NEP)-inhibitor sacubitrilat (LBQ657, (2R,4S)-4-(3-carboxypropanoylamino)-2-methyl-5-(4-phenylphenyl)-pentanoic acid) was obtained from BIOMOL GmbH (Hamburg, Germany), while Entresto pills (200 mg corresponding to 24 mg/26 mg sacubitril/valsartan per pill) containing the prodrug sacubitril (AHU377, 4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4oxobutanoic acid) (Figure 1) (Novartis, Basel, Switzerland) were purchased from a local pharmacy. For animal treatment (vide infra), whole pills were ground to a fine powder in a mortar, divided and suspended in tab water to individual 12 mg/200 mL doses of pill per animal [32 (link)].
Technetium-99m in the form of [^99mTc]NaTcO₄ was collected by elution of a [⁹⁹Mo]Mo/[^99mTc]Tc generator (Ultra-Technekow™ V4 Generator, Curium Pharma, Petten, The Netherlands). Indium-111 as an [¹¹¹In]InCl₃ solution was purchased from Curium Pharma (Petten, The Netherlands).

All chemicals were reagent-grade and were therefore used without further purification. The peptide conjugates DB7, DB13, and DB14 were synthesized on a solid support and obtained from PiChem (Graz, Austria). [Tyr⁴]BBN (Pyr–Gln–Arg–Tyr–Gly–Asn–Gln–Trp–Ala–Val–Gly–His–Leu–Met–NH₂) was purchased from Bachem (Bubendorf, Switzerland). PA (phosphoramidon disodium dehydrate, N-(α-rhamnopyranosyloxyhydroxyphosphinyl)-L-leucyl-L-tryptophan × 2Na × 2H₂O) was obtained from PeptaNova GmbH (Sandhausen, Germany).
Technetium-99m in the form of [^99mTc]NaTcO₄ was collected by elution of a [⁹⁹Mo]Mo/[^99mTc]Tc generator (Ultra-Technekow™ V4 Generator, Curium Pharma, Petten, The Netherlands), while [¹²⁵I]NaI in a solution of 10⁻⁵ M NaOH (10 μL) was purchased from Perkin Elmer (Waltham, MA, USA).