Slaveholders typically regarded the U.S. Constitution as their insurance policy against anything abolitionists might attempt. For that reason, if a respectable Southern leader spoke earnestly in favor of secession prior to the fall of 1859, I'm unaware of it. Most men would have reacted to the idea of secession as Robert E. Lee did. The idea of secession certainly would not have regarded favorably during the Nullification crisis of the 1830s, which concerned an unreasonable tariff, not slavery.
Nullification is one thing; secession is quite another.